1205:
bone tissues range from soft to stiff. The transduction of the stem cells into these cells types is not directed solely by chemokine cues and cell to cell signaling. The elasticity of the microenvironment can also affect the differentiation of mesenchymal stem cells (MSCs which originate in bone marrow.) When MSCs are placed on substrates of the same stiffness as brain, muscle and bone ECM, the MSCs take on properties of those respective cell types. Matrix sensing requires the cell to pull against the matrix at focal adhesions, which triggers a cellular mechano-transducer to generate a signal to be informed what force is needed to deform the matrix. To determine the key players in matrix-elasticity-driven lineage specification in MSCs, different matrix microenvironments were mimicked. From these experiments, it was concluded that focal adhesions of the MSCs were the cellular mechano-transducer sensing the differences of the matrix elasticity. The non-muscle myosin IIa-c isoforms generates the forces in the cell that lead to signaling of early commitment markers. Nonmuscle myosin IIa generates the least force increasing to non-muscle myosin IIc. There are also factors in the cell that inhibit non-muscle myosin II, such as
495:
45:
597:
1186:. In culture, Bmi1 mediates the Hedgehog pathway's ability to promote human mammary stem cell self-renewal. In both humans and mice, researchers showed Bmi1 to be highly expressed in proliferating immature cerebellar granule cell precursors. When Bmi1 was knocked out in mice, impaired cerebellar development resulted, leading to significant reductions in postnatal brain mass along with abnormalities in motor control and behavior. A separate study showed a significant decrease in neural stem cell proliferation along with increased astrocyte proliferation in Bmi null mice.
1347:
672:
1209:. This makes the cell effectively blind to the surrounding matrix. Researchers have achieved some success in inducing stem cell-like properties in HEK 239 cells by providing a soft matrix without the use of diffusing factors. The stem-cell properties appear to be linked to tension in the cells' actin network. One identified mechanism for matrix-induced differentiation is tension-induced proteins, which remodel chromatin in response to mechanical stretch. The RhoA pathway is also implicated in this process.
1066:, respectively. The acetyl group prevents Lysine's association with the negatively charged DNA backbone. Methylation is not as straightforward, as neither methylation nor demethylation consistently correlate with either gene activation or repression. However, certain methylations have been repeatedly shown to either activate or repress genes. The trimethylation of lysine 4 on histone 3 (H3K4Me3) is associated with gene activation, whereas trimethylation of lysine 27 on histone 3 represses genes
1009:-mediated methylation of cytosine residues in CpG dinucleotides maintains heritable repression by controlling DNA accessibility. The majority of CpG sites in embryonic stem cells are unmethylated and appear to be associated with H3K4me3-carrying nucleosomes. Upon differentiation, a small number of genes, including OCT4 and NANOG, are methylated and their promoters repressed to prevent their further expression. Consistently, DNA methylation-deficient embryonic stem cells rapidly enter
3868:
624:
1106:, and the majority of current knowledge about the subject consists of speculations on plausible candidate regulators of epigenetic remodeling. We will first discuss several major candidates thought to be involved in the induction and maintenance of both embryonic stem cells and their differentiated progeny, and then turn to one example of specific signaling pathways in which more direct evidence exists for its role in epigenetic change.
56:
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acquires enzymatic activity. The receptor then catalyzes reactions that phosphorylate other proteins, activating them. A cascade of phosphorylation reactions eventually activates a dormant transcription factor or cytoskeletal protein, thus contributing to the differentiation process in the target cell. Cells and tissues can vary in competence, their ability to respond to external signals.
904:. Second, the mechanisms of reprogramming (and by extension, differentiation) are very complex and cannot be easily duplicated, as seen by the significant number of differentially methylated regions between ES and iPS cell lines. Now that these two points have been established, we can examine some of the epigenetic mechanisms that are thought to regulate cellular differentiation.
1163:
Direct modulation of gene expression through modification of transcription factors plays a key role that must be distinguished from heritable epigenetic changes that can persist even in the absence of the original environmental signals. Only a few examples of signaling pathways leading to epigenetic changes that alter cell fate currently exist, and we will focus on one of them.
1058:. The epigenetic processes of histone methylation and acetylation, and their inverses demethylation and deacetylation primarily account for these changes. The effects of acetylation and deacetylation are more predictable. An acetyl group is either added to or removed from the positively charged Lysine residues in histones by enzymes called
997:) and promote gene activation through histone acetylation. PcG and TrxG complexes engage in direct competition and are thought to be functionally antagonistic, creating at differentiation and development-promoting loci what is termed a "bivalent domain" and rendering these genes sensitive to rapid induction or repression.
1204:
In order to fulfill the purpose of regenerating a variety of tissues, adult stems are known to migrate from their niches, adhere to new extracellular matrices (ECM) and differentiate. The ductility of these microenvironments are unique to different tissue types. The ECM surrounding brain, muscle and
722:
Signal induction refers to cascades of signaling events, during which a cell or tissue signals to another cell or tissue to influence its developmental fate. Yamamoto and
Jeffery investigated the role of the lens in eye formation in cave- and surface-dwelling fish, a striking example of induction.
1162:
The problem, of course, is that the candidacy of these signaling pathways was inferred primarily on the basis of their role in development and cellular differentiation. While epigenetic regulation is necessary for driving cellular differentiation, they are certainly not sufficient for this process.
1080:
During differentiation, stem cells change their gene expression profiles. Recent studies have implicated a role for nucleosome positioning and histone modifications during this process. There are two components of this process: turning off the expression of embryonic stem cell (ESC) genes, and the
992:
Alternately, upon receiving differentiation signals, PcG proteins are recruited to promoters of pluripotency transcription factors. PcG-deficient ES cells can begin differentiation but cannot maintain the differentiated phenotype. Simultaneously, differentiation and development-promoting genes are
983:
activity and resulting in transcriptional suppression. PcG knockout ES cells do not differentiate efficiently into the three germ layers, and deletion of the PRC1 and PRC2 genes leads to increased expression of lineage-affiliated genes and unscheduled differentiation. Presumably, PcG complexes are
174:
sequence itself. Metabolic composition, however, gets dramatically altered where stem cells are characterized by abundant metabolites with highly unsaturated structures whose levels decrease upon differentiation. Thus, different cells can have very different physical characteristics despite having
1101:
A final question to ask concerns the role of cell signaling in influencing the epigenetic processes governing differentiation. Such a role should exist, as it would be reasonable to think that extrinsic signaling can lead to epigenetic remodeling, just as it can lead to changes in gene expression
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and creates a single cell that has the potential to form an entire organism. In the first hours after fertilization, this cell divides into identical cells. In humans, approximately four days after fertilization and after several cycles of cell division, these cells begin to specialize, forming a
888:
However, upon examining methylation patterns more closely, the authors discovered 1175 regions of differential CG dinucleotide methylation between at least one ES or iPS cell line. By comparing these regions of differential methylation with regions of cytosine methylation in the original somatic
884:
in non-CG dinucleotides, while induced pluripotent cells possessed similar levels of methylation as embryonic stem cells, between 0.5 and 1.5%. Thus, consistent with their respective transcriptional activities, DNA methylation patterns, at least on the genomic level, are similar between ESCs and
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fate. Similarly, increased levels of Sox2 and decreased levels of Oct4 promote differentiation towards a neural ectodermal fate, with Sox2 inhibiting differentiation towards a mesendodermal fate. Regardless of the lineage cells differentiate down, suppression of NANOG has been identified as a
718:
pathways vary, these pathways often share the following general steps. A ligand produced by one cell binds to a receptor in the extracellular region of another cell, inducing a conformational change in the receptor. The shape of the cytoplasmic domain of the receptor changes, and the receptor
941:
and DNA methylation, to restrict or permit the transcription of target genes. While highly expressed, their levels require a precise balance to maintain pluripotency, perturbation of which will promote differentiation towards different lineages based on how the gene expression levels change.
1025:
of most cells of an organism is the same, the binding patterns of transcription factors and the corresponding gene expression patterns are different. To a large extent, differences in transcription factor binding are determined by the chromatin accessibility of their binding sites through
979:(PcG) family of proteins, catalyzes the di- and tri-methylation of histone H3 lysine 27 (H3K27me2/me3). By binding to the H3K27me2/3-tagged nucleosome, PRC1 (also a complex of PcG family proteins) catalyzes the mono-ubiquitinylation of histone H2A at lysine 119 (H2AK119Ub1), blocking
738:
because of an uneven distribution of regulatory molecules in the parent cell; the distinct cytoplasm that each daughter cell inherits results in a distinct pattern of differentiation for each daughter cell. A well-studied example of pattern formation by asymmetric divisions is
365:. The cells of the inner cell mass go on to form virtually all of the tissues of the human body. Although the cells of the inner cell mass can form virtually every type of cell found in the human body, they cannot form an organism. These cells are referred to as
757:, the 16 cells in the anterior hemisphere of a 32-cell embryo divide asymmetrically, each producing one large and one small daughter cell. The size of the cell at the end of all cell divisions determines whether it becomes a specialized germ or somatic cell.
345:—eggs and sperm—and thus are continuous through the generations. Stem cells, on the other hand, have the ability to divide for indefinite periods and to give rise to specialized cells. They are best described in the context of normal human development.
198:
and gut. During terminal differentiation, a precursor cell formerly capable of cell division permanently leaves the cell cycle, dismantles the cell cycle machinery and often expresses a range of genes characteristic of the cell's final function (e.g.
214:, which is the cell's ability to differentiate into other cell types. A greater potency indicates a larger number of cell types that can be derived. A cell that can differentiate into all cell types, including the placental tissue, is known as
1146:
are associated with the maintenance of mouse ESCs in an undifferentiated state. This is achieved through its activation of the Jak-STAT3 pathway, which has been shown to be necessary and sufficient towards maintaining mouse ESC pluripotency.
651:. Cell differentiation is thus a transition of a cell from one cell type to another and it involves a switch from one pattern of gene expression to another. Cellular differentiation during development can be understood as the result of a
723:
Through reciprocal transplants, Yamamoto and
Jeffery found that the lens vesicle of surface fish can induce other parts of the eye to develop in cave- and surface-dwelling fish, while the lens vesicle of the cave-dwelling fish cannot.
809:
In systems biology and mathematical modeling of gene regulatory networks, cell-fate determination is predicted to exhibit certain dynamics, such as attractor-convergence (the attractor can be an equilibrium point, limit cycle or
486:(listed from most distal (exterior) to proximal (interior)). The ectoderm ends up forming the skin and the nervous system, the mesoderm forms the bones and muscular tissue, and the endoderm forms the internal organ tissues.
889:
cells, 44-49% of differentially methylated regions reflected methylation patterns of the respective progenitor somatic cells, while 51-56% of these regions were dissimilar to both the progenitor and embryonic cell lines.
993:
activated by
Trithorax group (TrxG) chromatin regulators and lose their repression. TrxG proteins are recruited at regions of high transcriptional activity, where they catalyze the trimethylation of histone H3 lysine 4 (
1113:. The Wnt pathway is involved in all stages of differentiation, and the ligand Wnt3a can substitute for the overexpression of c-Myc in the generation of induced pluripotent stem cells. On the other hand, disruption of
822:
The first question that can be asked is the extent and complexity of the role of epigenetic processes in the determination of cell fate. A clear answer to this question can be seen in the 2011 paper by Lister R,
667:
gene expression, cellular differentiation is the result of a
Darwinian selective process occurring among cells. In this frame, protein and gene networks are the result of cellular processes and not their cause.
224:
are totipotent, while in plants, many differentiated cells can become totipotent with simple laboratory techniques. A cell that can differentiate into all cell types of the adult organism is known as
771:
Since each cell, regardless of cell type, possesses the same genome, determination of cell type must occur at the level of gene expression. While the regulation of gene expression can occur through
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In summary, the role of signaling in the epigenetic control of cell fate in mammals is largely unknown, but distinct examples exist that indicate the likely existence of further such mechanisms.
747:
molecules are an important type of intracellular differentiation control signal. The molecular and genetic basis of asymmetric cell divisions has also been studied in green algae of the genus
1139:
proteins. Depletion of growth factors promotes the differentiation of ESCs, while genes with bivalent chromatin can become either more restrictive or permissive in their transcription.
1193:. The mechanical signal is then epigenetically transduced via signal transduction systems (of which specific molecules such as Wnt are part) to result in differential gene expression.
1412:
Yanes, Oscar; Clark, Julie; Wong, Diana M.; Patti, Gary J.; Sánchez-Ruiz, Antonio; Benton, H. Paul; Trauger, Sunia A.; Desponts, Caroline; Ding, Sheng; Siuzdak, Gary (June 2010).
1093:(nucleosome remodelling and histone deacetylase) complex, giving an instance where methylation and acetylation are not discrete and mutually exclusive, but intertwined processes.
683:
conserved molecular processes are involved in the cellular mechanisms underlying these switches, in animal species these are very different from the well-characterized
130:
changes from one type to a differentiated one. Usually, the cell changes to a more specialized type. Differentiation happens multiple times during the development of a
3012:
Teif VB, Vainshtein Y, Caudron-Herger M, Mallm JP, Marth C, Höfer T, Rippe K (2012). "Genome-wide nucleosome positioning during embryonic stem cell development".
2963:
Bernstein BE, Kamal M, Lindblad-Toh K, Bekiranov S, Bailey DK, Huebert DJ, McMahon S, Karlsson EK, Kulbokas EJ, Gingeras TR, Schreiber SL, Lander ES (Jan 2005).
1189:
An alternative model of cellular differentiation during embryogenesis is that positional information is based on mechanical signalling by the cytoskeleton using
730:, divisions that give rise to daughter cells with distinct developmental fates. Asymmetric cell divisions can occur because of asymmetrically expressed maternal
838:
in their pluripotent properties, few epigenetic differences should exist between them. To test this prediction, the authors conducted whole-genome profiling of
117:
97:
77:
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in ESCs and iPSCs were methylated, the same was true of only 60% of CG dinucleotides in somatic cells. In addition, somatic cells possessed minimal levels of
655:. A regulatory gene and its cis-regulatory modules are nodes in a gene regulatory network; they receive input and create output elsewhere in the network. The
338:. Such cells, called somatic cells, make up most of the human body, such as skin and muscle cells. Cells differentiate to specialize for different functions.
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900:, as seen from the similar levels of cytosine methylation between induced pluripotent and embryonic stem cells, consistent with their respective patterns of
1123:
comprise the second major set of candidates of epigenetic regulators of cellular differentiation. These morphogens are crucial for development, and include
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through the activation or repression of different transcription factors. Little direct data is available concerning the specific signals that influence the
207:
for a muscle cell). Differentiation may continue to occur after terminal differentiation if the capacity and functions of the cell undergo further changes.
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2059:
301:
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in the laboratory, cells can change shape or may lose specific properties such as protein expression—which processes are also termed dedifferentiation.
893:-induced differentiation of iPSC lines saw transmission of 88% and 46% of hyper and hypo-methylated differentially methylated regions, respectively.
740:
659:
approach to developmental biology emphasizes the importance of investigating how developmental mechanisms interact to produce predictable patterns (
2881:
Krogan NJ, Dover J, Wood A, Schneider J, Heidt J, Boateng MA, Dean K, Ryan OW, Golshani A, Johnston M, Greenblatt JF, Shilatifard A (Mar 2003).
3848:
1527:
Schöler, Hans R. (2007). "The
Potential of Stem Cells: An Inventory". In Nikolaus Knoepffler; Dagmar Schipanski; Stefan Lorenz Sorgner (eds.).
1469:
Takahashi, K; Yamanaka, S (2006). "Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors".
2924:"Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity"
2883:"The Paf1 complex is required for histone H3 methylation by COMPASS and Dot1p: linking transcriptional elongation to histone methylation"
1050:
DNA-nucleosome interactions are characterized by two states: either tightly bound by nucleosomes and transcriptionally inactive, called
238:
in animals, though some groups report the presence of adult pluripotent cells. Virally induced expression of four transcription factors
2852:
3853:
1159:, in addition to its role as a morphogen, promotes embryonic stem cell differentiation and the self-renewal of somatic stem cells.
766:
710:. Many of the signal molecules that convey information from cell to cell during the control of cellular differentiation are called
3490:
Guilak, Farshid; Cohen, Daniel M.; Estes, Bradley T.; Gimble, Jeffrey M.; Liedtke, Wolfgang; Chen, Christopher S. (2009-07-02).
1962:"Dedifferentiation-associated changes in morphology and gene expression in primary human articular chondrocytes in cell culture"
2406:"Epigenetic and transcriptional regulations prime cell fate before division during human pluripotent stem cell differentiation"
2404:
Madrigal P, Deng S, Feng Y, Militi S, Goh KJ, Nibhani R, Grandy R, Osnato A, Ortmann D, Brown S, Pauklin S (January 25, 2023).
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2218:
1827:
1587:
1536:
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levels have been shown to precede germ layer fate selection. Increased levels of Oct4 and decreased levels of Sox2 promote a
17:
3267:
Leung C; et al. (2004). "Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas".
3058:
Whyte, W. A.; Bilodeau, S; Orlando, D. A.; Hoke, H. A.; Frampton, G. M.; Foster, C. T.; Cowley, S. M.; Young, R. A. (2012).
3674:
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Strother, Paul K.; Brasier, Martin D.; Wacey, David; Timpe, Leslie; Saunders, Martin; Wellman, Charles H. (13 April 2021).
1911:
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observed significant resemblance in methylation levels between embryonic and induced pluripotent cells. Around 80% of
1614:
570:, but others explain it as a natural part of the immune response that was lost to humans at some point of evolution.
3539:
3320:"Bmi1 loss produces an increase in astroglial cells and a decrease in neural stem cell population and proliferation"
361:. The blastocyst has an outer layer of cells, and inside this hollow sphere, there is a cluster of cells called the
585:. These manifestly dedifferentiated cells—now performing essentially as stem cells—could then redifferentiate into
1873:"Evidence for dedifferentiation and metaplasia in amphibian limb regeneration from inheritance of DNA methylation"
1755:"Bidirectional radial Ca(2+) activity regulates neurogenesis and migration during early cortical column formation"
272:
are more restricted than multipotent, but can still differentiate into a few closely related cell types. Finally,
1190:
618:
2087:
1135:(FGFs). TGFs and FGFs have been shown to sustain expression of OCT4, SOX2, and NANOG by downstream signaling to
3899:
929:– are highly expressed in undifferentiated embryonic stem cells and are necessary for the maintenance of their
831:
31:
318:. Each of the approximately 37.2 trillion (3.72x10) cells in an adult human has its own copy or copies of the
3712:
1039:
648:
388:(embryonic neural stem cells) that give rise to excitatory neurons in the fetal brain through the process of
2465:
420:(adult stem cells) from the bone marrow that give rise to stromal cells, fat cells, and types of bone cells
1304:"Solution of the chemical master equation by radial basis functions approximation with interface tracking"
896:
Two conclusions are readily apparent from this study. First, epigenetic processes are heavily involved in
3904:
3894:
1128:
1124:
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1143:
3220:"Hedgehog Signaling and Bmi-1 Regulate Self-renewal of Normal and Malignant Human Mammary Stem Cells"
1132:
1059:
753:, a model system for studying how unicellular organisms can evolve into multicellular organisms. In
162:, and responsiveness to signals. These changes are largely due to highly controlled modifications in
1857:
1346:
1117:, a component of the Wnt signaling pathway, leads to decreased proliferation of neural progenitors.
921:– the first two of which are used in induced pluripotent stem cell (iPSC) reprogramming, along with
3667:
901:
776:
727:
396:
183:
3564:
787:, the problem arises as to how this expression pattern is maintained over numerous generations of
3783:
2359:
976:
897:
696:
652:
150:
during tissue repair and during normal cell turnover. Some differentiation occurs in response to
2301:
Yamamoto, Y.; Jeffery, W. R. (2000). "Central Role for the Lens in Cave Fish Eye
Degeneration".
795:
processes play a crucial role in regulating the decision to adopt a stem, progenitor, or mature
59:
Cell-count distribution featuring cellular differentiation for three types of cells (progenitor
918:
772:
556:
416:
277:
131:
2692:"Genome-wide chromatin state transitions associated with developmental and environmental cues"
1369:
Slack, J.M.W. (2007). "Metaplasia and transdifferentiation: from pure biology to the clinic".
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responsible for transcriptionally repressing differentiation and development-promoting genes.
494:
3833:
3788:
3778:
3762:
2128:
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or because of signaling. In the former mechanism, distinct daughter cells are created during
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cell is one that can differentiate into multiple different, but closely related cell types.
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Kirk MM, A Ransick, SE Mcrae, DL Kirk; The relationship between cell size and cell fate in
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1923:
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where a differentiated cell reverts to an earlier developmental stage—usually as part of a
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genes. Patterns of DNA methylation in ESCs, iPSCs, somatic cells were compared. Lister R,
8:
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regions of pluripotency genes, thereby inhibiting their transcription. It interacts with
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784:
715:
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235:
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2643:"Pluripotency factors in embryonic stem cells regulate differentiation into germ layers"
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Several other signaling pathways are also considered to be primary candidates. Cytokine
1005:
Regulation of gene expression is further achieved through DNA methylation, in which the
446:
A pathway that is guided by the cell adhesion molecules consisting of four amino acids,
379:
that then give rise to functional cells. Examples of stem and progenitor cells include:
170:. With a few exceptions, cellular differentiation almost never involves a change in the
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3491:
3467:
3424:
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3319:
3300:
3244:
3219:
3151:
3092:
3059:
3037:
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2834:
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Meissner A (2010). "Epigenetic modifications in pluripotent and differentiated cells".
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2716:
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2615:
2590:
2551:
2519:"Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells"
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2022:
2002:
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1413:
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780:
269:
155:
102:
82:
62:
3195:
3171:"Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3"
3170:
3126:
Mohammad HP, Baylin SB (2010). "Linking cell signaling and the epigenetic machinery".
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2923:
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patterns in several human embryonic stem cell (ESC), iPSC, and progenitor cell lines.
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44:
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1335:
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856:, and foreskin fibroblasts were reprogrammed into induced pluripotent state with the
811:
540:
384:
3405:
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Yamamoto Y and WR Jeffery; Central role for the lens in cave fish eye degeneration.
3793:
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2965:"Genomic maps and comparative analysis of histone modifications in human and mouse"
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2768:
2711:
2703:
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2610:
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2500:
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2466:"Branching and oscillations in the epigenetic landscape of cell-fate determination"
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2014:
1973:
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3492:"Control of Stem Cell Fate by Physical Interactions with the Extracellular Matrix"
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3702:
3420:
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Thomson, M; Liu, S. J.; Zou, L. N.; Smith, Z; Meissner, A; Ramanathan, S (2011).
2322:
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1054:, or loosely bound and usually, but not always, transcriptionally active, called
1051:
839:
656:
632:
376:
362:
191:
163:
143:
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is covering a given genomic binding site or not. This can be determined using a
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Some hypothesize that dedifferentiation is an aberration that likely results in
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3507:
3388:
3371:
2981:
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2707:
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1939:
1814:. Current Topics in Microbiology and Immunology. Vol. 280. pp. 1–70.
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2003:"Cellular origin of cancer: dedifferentiation or stem cell maturation arrest?"
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Slack, J.M.W. (2013) Essential
Developmental Biology. Wiley-Blackwell, Oxford.
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3625:
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3060:"Enhancer decommissioning by LSD1 during embryonic stem cell differentiation"
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788:
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514:
439:
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147:
38:
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3592:"A possible billion-year-old holozoan with differentiated multicellularity"
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1987:
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3540:"Billion-year-old fossil reveals missing link in the evolution of animals"
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is involved in the proliferation and self-renewal of stem cells. Finally,
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1055:
955:
853:
735:
601:
529:
401:
373:
366:
265:
226:
167:
3288:
3083:
2542:
2026:
1491:
1035:
803:
792:
695:. Specifically, cell differentiation in animals is highly dependent on
664:
623:
600:
Diagram exposing several methods used to revert adult somatic cells to
586:
525:
498:
471:
455:
358:
335:
330:, that lack nuclei in their fully differentiated state. Most cells are
323:
261:
221:
216:
159:
3025:
1912:"Dedifferentiation and Regeneration in Bryophytes: A Selective Review"
1657:"Evolution of the neocortex: a perspective from developmental biology"
3683:
2822:
2075:
1103:
1075:
1010:
934:
800:
796:
680:
663:). However, an alternative view has been proposed recently. Based on
590:
574:
552:
510:
424:
315:
307:
273:
195:
154:
exposure. Differentiation dramatically changes a cell's size, shape,
127:
48:
2355:"The relationship between cell size and cell fate in Volvox carteri"
2018:
1672:
1382:
1237:
with two types of cells, shows that the evolution of differentiated
954:
fate, with Oct4 actively suppressing genes associated with a neural
429:(progenitor cells) that give rise to the various types of skin cells
276:
cells can differentiate into only one cell type, but are capable of
2962:
2213:(8th ed.). Sunderland, Mass: Sinauer Associates. p. 147.
2168:
1414:"Metabolic oxidation regulates embryonic stem cell differentiation"
1171:
890:
877:
688:
483:
479:
475:
467:
447:
409:
231:
3011:
1228:
1224:
1166:
Expression of Shh (Sonic hedgehog) upregulates the production of
994:
846:
834:. As induced pluripotent stem cells (iPSCs) are thought to mimic
692:
644:
582:
451:
342:
331:
151:
1960:
Schnabel M, Marlovits S, Eckhoff G, et al. (January 2002).
284:, the level of cellular differentiation is used as a measure of
3745:
3735:
2208:
749:
684:
636:
578:
567:
559:
process. Dedifferentiation also occurs in plant cells. And, in
459:
319:
285:
200:
176:
135:
1081:
activation of cell fate genes. Lysine specific demethylase 1 (
933:. It is thought that they achieve this through alterations in
3740:
3652:
3639:
2246:
Rudel and Sommer; The evolution of developmental mechanisms.
1278:
943:
926:
828:
349:
260:) is sufficient to create pluripotent (iPS) cells from adult
248:
204:
3370:
Engler, AJ; Sen, S; Sweeney, HL; Discher, DE (August 2006).
2353:
Kirk, M. M.; Ransick, A.; McRae, S. E.; Kirk, D. L. (1993).
1630:
D. Binder, Marc; Hirokawa, Nobutaka; Windhorst, Uwe (2009).
306:
Three basic categories of cells make up the mammalian body:
30:"Cell differentiation" redirects here. For the journal, see
3565:"Billion-year-old fossil found preserved in Torridon rocks"
3372:"Matrix Elasticity Directs Stem Cell Lineage Specification"
1871:
Casimir CM, Gates PB, Patient RK, Brockes JP (1988-12-01).
1810:
1179:
1175:
1167:
1090:
1082:
972:
947:
922:
865:
861:
857:
850:
640:
548:
372:
Pluripotent stem cells undergo further specialization into
253:
243:
239:
1870:
1629:
1096:
292:" is a marker of how differentiated a cell in a tumor is.
142:
and cell types. Differentiation continues in adulthood as
55:
3589:
2152:"Cell differentiation: what have we learned in 50 years?"
2107:
869:
744:
647:. Each cell type is defined by its particular pattern of
543:, or integration, is a cellular process seen in the more
186:, is of importance in some tissues, including vertebrate
171:
3057:
2880:
1959:
1151:
can induce differentiation of human and mouse ESCs, and
341:
Germ line cells are any line of cells that give rise to
27:
Transformation of a stem cell to a more specialized cell
3369:
3168:
1582:(4th ed.). New York: W. H. Freeman. Section 14.2.
3489:
2403:
2110:"Gene regulation: gene control network in development"
1045:
912:
907:
726:
Other important mechanisms fall under the category of
1284:
List of human cell types derived from the germ layers
962:
438:(progenitor cells) that contribute to differentiated
105:
85:
65:
2352:
1301:
2921:
2588:
1704:Lui, JH; Hansen, DV; Kriegstein, AR (8 July 2011).
1703:
1609:. I.K. International Publishing House. p. 22.
1411:
1241:, possibly but not necessarily of animal lineages,
1034:. In particular, it is important to know whether a
817:
524:, showing a few blood vessels, (center of image). (
302:
List of distinct cell types in the adult human body
210:Among dividing cells, there are multiple levels of
2640:
1706:"Development and evolution of the human neocortex"
1575:
987:
675:An overview of major signal transduction pathways.
581:analog, has proven to induce dedifferentiation in
111:
91:
71:
2584:
2582:
2580:
2578:
2576:
2574:
2572:
2570:
2463:
1468:
1170:, a component of the PcG complex that recognizes
3886:
3418:
2922:Ng HH, Robert F, Young RA, Struhl K (Mar 2003).
2591:"Epigenetic control of embryonic stem cell fate"
1753:Rash, BG; Ackman, JB; Rakic, P (February 2016).
1526:
706:Cellular differentiation is often controlled by
182:A specialized type of differentiation, known as
51:differentiation into various animal tissue types
3429:Proceedings of the National Academy of Sciences
2300:
1752:
3849:Stem cell laws and policy in the United States
3169:Niwa H, Burdon T, Chambers I, Smith A (1998).
3125:
2567:
2464:Rabajante JF, Babierra AL (January 30, 2015).
1302:Kryven, I.; Röblitz, S.; Schütte, Ch. (2015).
1199:
691:, and even from those of the animals' closest
3668:
3053:
3051:
2743:
2636:
2634:
917:Three transcription factors, OCT4, SOX2, and
220:. In mammals, only the zygote and subsequent
2956:
2915:
2874:
2473:Progress in Biophysics and Molecular Biology
1174:. This occurs in a Gli-dependent manner, as
959:necessary prerequisite for differentiation.
3121:
3119:
3117:
3115:
3113:
3111:
2804:
2802:
2800:
2739:
2737:
2735:
2291:
2289:
2254:"The evolution of developmental mechanisms"
2251:
3675:
3661:
3048:
3005:
2808:
2631:
2209:Knisely, Karen; Gilbert, Scott F. (2009).
1522:
1520:
1518:
631:Each specialized cell type in an organism
3615:
3515:
3466:
3448:
3387:
3343:
3243:
3194:
3091:
2980:
2939:
2898:
2780:
2715:
2666:
2614:
2550:
2512:
2510:
2440:
2380:
2269:
2185:
2167:
2108:Ben-Tabou de-Leon S, Davidson EH (2007).
2057:
2034:
1977:
1809:
1786:
1729:
1680:
1490:
1445:
1329:
1319:
1016:
3854:Epigenetics in stem cell differentiation
3317:
3108:
2797:
2732:
2516:
2286:
2242:
2240:
2238:
2236:
2234:
2232:
2230:
2129:10.1146/annurev.biophys.35.040405.102002
1909:
767:Epigenetics in stem cell differentiation
670:
622:
595:
493:
462:, is created as the cellular blastomere
54:
43:
3266:
2689:
2202:
1864:
1803:
1515:
1212:
1097:Role of signaling in epigenetic control
295:
146:divide and create fully differentiated
14:
3887:
3311:
2507:
2149:
2143:
2101:
2060:"Stem cells from differentiated cells"
2000:
1573:
1529:Humanbiotechnology as Social Challenge
1259:Interbilayer Forces in Membrane Fusion
827:on aberrant epigenomic programming in
627:Mechanisms of cellular differentiation
3656:
3365:
3363:
3260:
3217:
2683:
2227:
1654:
1602:
1371:Nature Reviews Molecular Cell Biology
1368:
1243:occurred at least 1 billion years ago
799:This section will focus primarily on
760:
119:) exposed to pro-osteoblast stimulus.
3425:"Actin stress in cell reprogramming"
3162:
2337:
489:
3211:
2589:Christophersen NS, Helin K (2010).
1812:Regeneration: Stem Cells and Beyond
1085:) is thought to prevent the use of
1046:Histone acetylation and methylation
913:Pioneer factors (Oct4, Sox2, Nanog)
908:Mechanisms of epigenetic regulation
714:. Although the details of specific
643:that constitute the genome of that
573:A newly discovered molecule dubbed
404:that give rise to red blood cells,
24:
3360:
1531:. Ashgate Publishing. p. 28.
1295:
1000:
963:Polycomb repressive complex (PRC2)
741:body axis patterning in Drosophila
25:
3916:
2252:Rudel, D.; Sommer, R. J. (2003).
357:hollow sphere of cells, called a
3867:
3866:
3638:
2485:10.1016/j.pbiomolbio.2015.01.006
1553:"NCI Dictionary of Cancer Terms"
1345:
1182:are downstream effectors of the
1069:
818:Importance of epigenetic control
3583:
3557:
3532:
3483:
3412:
2845:
2457:
2397:
2051:
1994:
1953:
1903:
1746:
1697:
1648:
1623:
1191:Embryonic differentiation waves
1013:upon in vitro differentiation.
988:Trithorax group proteins (TrxG)
619:Embryonic differentiation waves
547:life forms in animals, such as
505:, (at left edge of image). + A
334:; they have two copies of each
3713:Induced pluripotent stem cells
3682:
3336:10.1523/JNEUROSCI.3452-04.2005
3318:Zencak D; et al. (2005).
2744:Guenther MG, Young RA (2010).
2517:Lister R; et al. (2011).
2156:Journal of Theoretical Biology
2117:Annu Rev Biophys Biomol Struct
1936:10.1080/0028825x.1971.10430231
1596:
1567:
1545:
1462:
1405:
1362:
1353:
832:induced pluripotent stem cells
32:Cell Differentiation (journal)
13:
1:
3423:; Meng, Fanjie (2014-12-09).
3236:10.1158/0008-5472.CAN-06-0054
2941:10.1016/S1097-2765(03)00092-3
2900:10.1016/S1097-2765(03)00091-1
2853:"Chromatin Immuprecipitation"
2690:Zhu, J.; et al. (2013).
2271:10.1016/S0012-1606(03)00353-1
1916:New Zealand Journal of Botany
1289:
1109:The first major candidate is
1040:chromatin immunoprecipitation
973:Polycomb repressive complex 2
612:
2323:10.1126/science.289.5479.631
1661:Nature Reviews. Neuroscience
1632:Encyclopedia of Neuroscience
1606:Textbook of Human Embryology
1223:A billion-years-old, likely
975:, one of two classes of the
400:(adult stem cells) from the
134:as it changes from a simple
7:
3218:Liu S; et al. (2006).
1820:10.1007/978-3-642-18846-6_1
1555:. National Cancer Institute
1252:
1200:Effect of matrix elasticity
1144:leukemia inhibitory factors
1129:transforming growth factors
1125:bone morphogenetic proteins
942:Differential regulation of
699:of regulatory proteins and
517:, (right edge of image). +
10:
3921:
3508:10.1016/j.stem.2009.06.016
3389:10.1016/j.cell.2006.06.044
2982:10.1016/j.cell.2005.01.001
2746:"Repressive Transcription"
2708:10.1016/j.cell.2012.12.033
2659:10.1016/j.cell.2011.05.017
2433:10.1038/s41467-023-36116-9
2299:289 (5479), 631-633, 2000
2187:10.1016/j.jtbi.2019.110031
2150:Newman, Stuart A. (2020).
1722:10.1016/j.cell.2011.06.030
1483:10.1016/j.cell.2006.07.024
1216:
1184:Hedgehog signaling pathway
1073:
1060:histone acetyltransferases
764:
685:gene regulatory mechanisms
616:
348:Development begins when a
299:
126:is the process in which a
36:
29:
3862:
3816:
3721:
3690:
3617:10.1016/j.cub.2021.03.051
1655:Rakic, P (October 2009).
1321:10.1186/s12918-015-0210-y
1133:fibroblast growth factors
777:trans-regulatory elements
728:asymmetric cell divisions
649:regulated gene expression
3824:Cellular differentiation
3419:Guo, Jun; Wang, Yuexiu;
2058:Tsonis PA (April 2004).
2007:Environ. Health Perspect
2001:Sell S (December 1993).
732:cytoplasmic determinants
697:biomolecular condensates
466:from the single-layered
397:Hematopoietic stem cells
230:. Such cells are called
184:terminal differentiation
124:Cellular differentiation
37:Not to be confused with
3784:Hematopoietic stem cell
3450:10.1073/pnas.1411683111
2773:10.1126/science.1193995
2360:Journal of Cell Biology
2349:Journal of Cell Biology
1574:Lodish, Harvey (2000).
1418:Nature Chemical Biology
1249:rather than the ocean.
1245:and possibly mainly in
898:cell fate determination
653:gene regulatory network
474:in mammals, namely the
138:to a complex system of
3187:10.1101/gad.12.13.2048
1979:10.1053/joca.2001.0482
1779:10.1126/sciadv.1501733
1578:Molecular Cell Biology
1017:Nucleosome positioning
676:
628:
609:
537:
503:some dedifferentiation
417:Mesenchymal stem cells
132:multicellular organism
120:
113:
93:
73:
52:
3900:Developmental biology
3834:Stem cell controversy
3789:Mesenchymal stem cell
3779:Endothelial stem cell
2413:Nature Communications
2373:10.1083/jcb.123.1.191
2258:Developmental Biology
2248:Developmental Biology
2211:Developmental Biology
1889:10.1242/dev.104.4.657
1111:Wnt signaling pathway
1074:Further information:
1007:DNA methyltransferase
693:unicellular relatives
674:
626:
599:
497:
470:to the three primary
234:in higher plants and
166:and are the study of
114:
94:
74:
58:
47:
18:Undifferentiated cell
3698:Embryonic stem cells
3602:(12): 2658–2665.e2.
3140:10.1038/nbt1010-1033
2857:www.bio.brandeis.edu
2607:10.1084/jem.20101438
1603:Kumar, Rani (2008).
1430:10.1038/nchembio.364
1269:Lipid bilayer fusion
1213:Evolutionary history
1028:histone modification
939:histone modification
882:cytosine methylation
836:embryonic stem cells
519:Fully differentiated
472:layers of germ cells
296:Mammalian cell types
236:embryonic stem cells
103:
83:
63:
3758:Embryonic stem cell
3608:2021CBio...31E2658S
3441:2014PNAS..111E5252G
3435:(49): E5252–E5261.
3289:10.1038/nature02385
3281:2004Natur.428..337L
3084:10.1038/nature10805
3076:2012Natur.482..221W
3014:Nat Struct Mol Biol
2765:2010Sci...329..150G
2543:10.1038/nature09798
2535:2011Natur.471...68L
2425:2023NatCo..14..405M
2351:123, 191-208, 1993
2315:2000Sci...289..631Y
2178:2020JThBi.48510031N
1928:1971NZJB....9..689G
1771:2016SciA....2E1733R
1308:BMC Systems Biology
1064:histone deactylases
937:structure, such as
791:. As it turns out,
779:including a gene's
716:signal transduction
509:component, showing
3905:Induced stem cells
3895:Cellular processes
2013:(Suppl 5): 15–26.
1966:Osteoarthr. Cartil
1274:Cell-cell fusogens
814:) or oscillatory.
761:Epigenetic control
677:
629:
610:
538:
385:Radial glial cells
232:meristematic cells
160:metabolic activity
156:membrane potential
121:
109:
99:, and chondrocyte
89:
69:
53:
3882:
3881:
3829:Stem cell therapy
3708:Cancer stem cells
3026:10.1038/nsmb.2419
2309:(5479): 631–633.
2250:264, 15-37, 2003
2220:978-0-87893-371-6
1910:Giles KL (1971).
1829:978-3-540-02238-1
1589:978-0-7167-3136-8
1538:978-0-7546-5755-2
1234:Bicellum brasieri
1091:Mi-2/NuRD complex
981:RNA polymerase II
812:strange attractor
541:Dedifferentiation
490:Dedifferentiation
406:white blood cells
270:Oligopotent cells
112:{\displaystyle x}
92:{\displaystyle y}
72:{\displaystyle z}
16:(Redirected from
3912:
3870:
3869:
3817:Related articles
3794:Neural stem cell
3703:Adult stem cells
3677:
3670:
3663:
3654:
3653:
3648:
3643:Available under
3642:
3637:
3619:
3587:
3581:
3580:
3578:
3576:
3561:
3555:
3554:
3552:
3550:
3536:
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3519:
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3481:
3480:
3470:
3452:
3421:Sachs, Frederick
3416:
3410:
3409:
3391:
3367:
3358:
3357:
3347:
3315:
3309:
3308:
3275:(6980): 337–41.
3264:
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3257:
3247:
3215:
3209:
3208:
3198:
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3160:
3159:
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2953:
2943:
2919:
2913:
2912:
2902:
2878:
2872:
2871:
2869:
2868:
2859:. Archived from
2849:
2843:
2842:
2823:10.1038/nbt.1684
2806:
2795:
2794:
2784:
2750:
2741:
2730:
2729:
2719:
2687:
2681:
2680:
2670:
2638:
2629:
2628:
2618:
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2565:
2564:
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2505:
2504:
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2455:
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2334:
2293:
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2283:
2273:
2244:
2225:
2224:
2206:
2200:
2199:
2189:
2171:
2147:
2141:
2140:
2123:(191): 191–212.
2114:
2105:
2099:
2098:
2096:
2095:
2086:. Archived from
2076:10.1124/mi.4.2.4
2055:
2049:
2048:
2038:
1998:
1992:
1991:
1981:
1957:
1951:
1950:
1948:
1947:
1938:. Archived from
1907:
1901:
1900:
1868:
1862:
1861:
1855:
1851:
1849:
1841:
1807:
1801:
1800:
1790:
1759:Science Advances
1750:
1744:
1743:
1733:
1701:
1695:
1694:
1684:
1652:
1646:
1645:
1627:
1621:
1620:
1600:
1594:
1593:
1581:
1571:
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1564:
1562:
1560:
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1524:
1513:
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1494:
1466:
1460:
1459:
1449:
1409:
1403:
1402:
1366:
1360:
1357:
1351:
1350:
1349:
1343:
1333:
1323:
1299:
1264:Fusion mechanism
1247:freshwater lakes
1239:multicellularity
967:In the realm of
878:CG dinucleotides
377:progenitor cells
258:Yamanaka factors
251:
144:adult stem cells
118:
116:
115:
110:
98:
96:
95:
90:
78:
76:
75:
70:
21:
3920:
3919:
3915:
3914:
3913:
3911:
3910:
3909:
3885:
3884:
3883:
3878:
3858:
3812:
3775:Progenitor cell
3717:
3686:
3681:
3651:
3596:Current Biology
3588:
3584:
3574:
3572:
3563:
3562:
3558:
3548:
3546:
3538:
3537:
3533:
3488:
3484:
3417:
3413:
3368:
3361:
3330:(24): 5774–83.
3316:
3312:
3265:
3261:
3230:(12): 6063–71.
3216:
3212:
3181:(13): 2048–60.
3167:
3163:
3124:
3109:
3070:(7384): 221–5.
3056:
3049:
3020:(11): 1185–92.
3010:
3006:
2961:
2957:
2920:
2916:
2879:
2875:
2866:
2864:
2851:
2850:
2846:
2817:(10): 1079–88.
2807:
2798:
2759:(5988): 150–1.
2748:
2742:
2733:
2688:
2684:
2639:
2632:
2601:(11): 2287–95.
2587:
2568:
2529:(7336): 68–73.
2515:
2508:
2468:
2462:
2458:
2408:
2402:
2398:
2342:
2338:
2294:
2287:
2245:
2228:
2221:
2207:
2203:
2148:
2144:
2112:
2106:
2102:
2093:
2091:
2056:
2052:
2019:10.2307/3431838
1999:
1995:
1958:
1954:
1945:
1943:
1908:
1904:
1869:
1865:
1853:
1852:
1843:
1842:
1830:
1808:
1804:
1765:(2): e1501733.
1751:
1747:
1702:
1698:
1673:10.1038/nrn2719
1653:
1649:
1642:
1628:
1624:
1617:
1601:
1597:
1590:
1572:
1568:
1558:
1556:
1551:
1550:
1546:
1539:
1525:
1516:
1467:
1463:
1410:
1406:
1383:10.1038/nrm2146
1367:
1363:
1358:
1354:
1344:
1300:
1296:
1292:
1255:
1221:
1215:
1202:
1153:Notch signaling
1099:
1078:
1072:
1052:heterochromatin
1048:
1032:pioneer factors
1019:
1003:
1001:DNA methylation
990:
965:
915:
910:
840:DNA methylation
820:
769:
763:
703:DNA sequences.
657:systems biology
621:
615:
492:
435:satellite cells
363:inner cell mass
328:red blood cells
322:except certain
304:
298:
247:
192:striated muscle
164:gene expression
104:
101:
100:
84:
81:
80:
64:
61:
60:
42:
35:
28:
23:
22:
15:
12:
11:
5:
3918:
3908:
3907:
3902:
3897:
3880:
3879:
3877:
3876:
3863:
3860:
3859:
3857:
3856:
3851:
3846:
3844:Stem cell laws
3841:
3839:Stem cell line
3836:
3831:
3826:
3820:
3818:
3814:
3813:
3811:
3810:
3809:
3808:
3806:Precursor cell
3798:
3797:
3796:
3791:
3786:
3781:
3767:
3766:
3765:
3760:
3750:
3749:
3748:
3743:
3738:
3727:
3725:
3719:
3718:
3716:
3715:
3710:
3705:
3700:
3694:
3692:
3688:
3687:
3680:
3679:
3672:
3665:
3657:
3650:
3649:
3582:
3556:
3531:
3496:Cell Stem Cell
3482:
3411:
3382:(4): 677–689.
3359:
3310:
3259:
3210:
3161:
3134:(10): 1033–8.
3128:Nat Biotechnol
3107:
3047:
3004:
2955:
2928:Molecular Cell
2914:
2887:Molecular Cell
2873:
2844:
2811:Nat Biotechnol
2796:
2731:
2702:(3): 642–654.
2682:
2630:
2566:
2506:
2479:(2–3): 240–9.
2456:
2396:
2367:(1): 191–208.
2345:Volvox carteri
2336:
2285:
2226:
2219:
2201:
2142:
2100:
2050:
1993:
1952:
1902:
1883:(4): 657–668.
1863:
1854:|journal=
1828:
1802:
1745:
1696:
1667:(10): 724–35.
1647:
1641:978-3540237358
1640:
1622:
1615:
1595:
1588:
1566:
1544:
1537:
1514:
1461:
1424:(6): 411–417.
1404:
1377:(5): 369–378.
1361:
1352:
1293:
1291:
1288:
1287:
1286:
1281:
1276:
1271:
1266:
1261:
1254:
1251:
1214:
1211:
1201:
1198:
1157:Sonic hedgehog
1121:Growth factors
1098:
1095:
1071:
1068:
1047:
1044:
1018:
1015:
1002:
999:
989:
986:
977:Polycomb group
969:gene silencing
964:
961:
914:
911:
909:
906:
819:
816:
765:Main article:
762:
759:
755:Volvox carteri
712:growth factors
708:cell signaling
681:evolutionarily
614:
611:
532:prepared with
522:adipose tissue
513:and increased
507:differentiated
491:
488:
464:differentiates
444:
443:
430:
421:
413:
393:
352:fertilizes an
297:
294:
288:progression. "
188:nervous system
148:daughter cells
108:
88:
68:
26:
9:
6:
4:
3:
2:
3917:
3906:
3903:
3901:
3898:
3896:
3893:
3892:
3890:
3875:
3874:
3865:
3864:
3861:
3855:
3852:
3850:
3847:
3845:
3842:
3840:
3837:
3835:
3832:
3830:
3827:
3825:
3822:
3821:
3819:
3815:
3807:
3804:
3803:
3802:
3799:
3795:
3792:
3790:
3787:
3785:
3782:
3780:
3776:
3773:
3772:
3771:
3768:
3764:
3761:
3759:
3756:
3755:
3754:
3751:
3747:
3744:
3742:
3739:
3737:
3734:
3733:
3732:
3729:
3728:
3726:
3724:
3720:
3714:
3711:
3709:
3706:
3704:
3701:
3699:
3696:
3695:
3693:
3691:Sources/types
3689:
3685:
3678:
3673:
3671:
3666:
3664:
3659:
3658:
3655:
3646:
3641:
3635:
3631:
3627:
3623:
3618:
3613:
3609:
3605:
3601:
3597:
3593:
3586:
3570:
3566:
3560:
3545:
3541:
3535:
3527:
3523:
3518:
3513:
3509:
3505:
3501:
3497:
3493:
3486:
3478:
3474:
3469:
3464:
3460:
3456:
3451:
3446:
3442:
3438:
3434:
3430:
3426:
3422:
3415:
3407:
3403:
3399:
3395:
3390:
3385:
3381:
3377:
3373:
3366:
3364:
3355:
3351:
3346:
3341:
3337:
3333:
3329:
3325:
3321:
3314:
3306:
3302:
3298:
3294:
3290:
3286:
3282:
3278:
3274:
3270:
3263:
3255:
3251:
3246:
3241:
3237:
3233:
3229:
3225:
3221:
3214:
3206:
3202:
3197:
3192:
3188:
3184:
3180:
3176:
3172:
3165:
3157:
3153:
3149:
3145:
3141:
3137:
3133:
3129:
3122:
3120:
3118:
3116:
3114:
3112:
3103:
3099:
3094:
3089:
3085:
3081:
3077:
3073:
3069:
3065:
3061:
3054:
3052:
3043:
3039:
3035:
3031:
3027:
3023:
3019:
3015:
3008:
3000:
2996:
2992:
2988:
2983:
2978:
2975:(2): 169–81.
2974:
2970:
2966:
2959:
2951:
2947:
2942:
2937:
2934:(3): 709–19.
2933:
2929:
2925:
2918:
2910:
2906:
2901:
2896:
2892:
2888:
2884:
2877:
2863:on 2017-11-25
2862:
2858:
2854:
2848:
2840:
2836:
2832:
2828:
2824:
2820:
2816:
2812:
2805:
2803:
2801:
2792:
2788:
2783:
2778:
2774:
2770:
2766:
2762:
2758:
2754:
2747:
2740:
2738:
2736:
2727:
2723:
2718:
2713:
2709:
2705:
2701:
2697:
2693:
2686:
2678:
2674:
2669:
2664:
2660:
2656:
2653:(6): 875–89.
2652:
2648:
2644:
2637:
2635:
2626:
2622:
2617:
2612:
2608:
2604:
2600:
2596:
2592:
2585:
2583:
2581:
2579:
2577:
2575:
2573:
2571:
2562:
2558:
2553:
2548:
2544:
2540:
2536:
2532:
2528:
2524:
2520:
2513:
2511:
2502:
2498:
2494:
2490:
2486:
2482:
2478:
2474:
2467:
2460:
2452:
2448:
2443:
2438:
2434:
2430:
2426:
2422:
2418:
2414:
2407:
2400:
2392:
2388:
2383:
2378:
2374:
2370:
2366:
2362:
2361:
2356:
2350:
2346:
2340:
2332:
2328:
2324:
2320:
2316:
2312:
2308:
2304:
2298:
2292:
2290:
2281:
2277:
2272:
2267:
2263:
2259:
2255:
2249:
2243:
2241:
2239:
2237:
2235:
2233:
2231:
2222:
2216:
2212:
2205:
2197:
2193:
2188:
2183:
2179:
2175:
2170:
2165:
2161:
2157:
2153:
2146:
2138:
2134:
2130:
2126:
2122:
2118:
2111:
2104:
2090:on 2016-05-23
2089:
2085:
2081:
2077:
2073:
2069:
2065:
2061:
2054:
2046:
2042:
2037:
2032:
2028:
2024:
2020:
2016:
2012:
2008:
2004:
1997:
1989:
1985:
1980:
1975:
1971:
1967:
1963:
1956:
1942:on 2008-12-04
1941:
1937:
1933:
1929:
1925:
1922:(4): 689–94.
1921:
1917:
1913:
1906:
1898:
1894:
1890:
1886:
1882:
1878:
1874:
1867:
1859:
1847:
1839:
1835:
1831:
1825:
1821:
1817:
1813:
1806:
1798:
1794:
1789:
1784:
1780:
1776:
1772:
1768:
1764:
1760:
1756:
1749:
1741:
1737:
1732:
1727:
1723:
1719:
1715:
1711:
1707:
1700:
1692:
1688:
1683:
1678:
1674:
1670:
1666:
1662:
1658:
1651:
1643:
1637:
1633:
1626:
1618:
1616:9788190675710
1612:
1608:
1607:
1599:
1591:
1585:
1580:
1579:
1570:
1554:
1548:
1540:
1534:
1530:
1523:
1521:
1519:
1510:
1506:
1502:
1498:
1493:
1488:
1484:
1480:
1477:(4): 663–76.
1476:
1472:
1465:
1457:
1453:
1448:
1443:
1439:
1435:
1431:
1427:
1423:
1419:
1415:
1408:
1400:
1396:
1392:
1388:
1384:
1380:
1376:
1372:
1365:
1356:
1348:
1341:
1337:
1332:
1327:
1322:
1317:
1313:
1309:
1305:
1298:
1294:
1285:
1282:
1280:
1277:
1275:
1272:
1270:
1267:
1265:
1262:
1260:
1257:
1256:
1250:
1248:
1244:
1240:
1236:
1235:
1230:
1226:
1220:
1210:
1208:
1197:
1194:
1192:
1187:
1185:
1181:
1177:
1173:
1169:
1164:
1160:
1158:
1154:
1150:
1149:Retinoic acid
1145:
1140:
1138:
1134:
1130:
1126:
1122:
1118:
1116:
1112:
1107:
1105:
1094:
1092:
1088:
1084:
1077:
1070:In stem cells
1067:
1065:
1061:
1057:
1053:
1043:
1041:
1037:
1033:
1029:
1024:
1014:
1012:
1008:
998:
996:
985:
982:
978:
974:
970:
960:
957:
953:
952:mesendodermal
949:
945:
940:
936:
932:
928:
924:
920:
905:
903:
902:transcription
899:
894:
892:
886:
883:
879:
875:
871:
867:
863:
859:
855:
852:
848:
843:
841:
837:
833:
830:
826:
815:
813:
807:
805:
802:
798:
794:
790:
789:cell division
786:
782:
778:
774:
768:
758:
756:
752:
751:
746:
742:
737:
733:
729:
724:
720:
717:
713:
709:
704:
702:
698:
694:
690:
686:
682:
673:
669:
666:
662:
661:morphogenesis
658:
654:
650:
646:
642:
638:
634:
625:
620:
607:
603:
598:
594:
592:
588:
584:
580:
576:
571:
569:
564:
562:
558:
554:
550:
546:
542:
535:
534:H&E stain
531:
527:
523:
520:
516:
512:
508:
504:
500:
496:
487:
485:
481:
477:
473:
469:
465:
461:
457:
453:
449:
441:
440:muscle tissue
437:
436:
431:
428:
426:
422:
419:
418:
414:
411:
407:
403:
399:
398:
394:
391:
387:
386:
382:
381:
380:
378:
375:
370:
368:
364:
360:
355:
351:
346:
344:
339:
337:
333:
329:
325:
321:
317:
313:
312:somatic cells
309:
303:
293:
291:
287:
283:
282:cytopathology
279:
275:
271:
267:
263:
259:
255:
250:
245:
241:
237:
233:
229:
228:
223:
219:
218:
213:
208:
206:
202:
197:
193:
189:
185:
180:
178:
173:
169:
165:
161:
157:
153:
149:
145:
141:
137:
133:
129:
125:
106:
86:
79:, osteoblast
66:
57:
50:
46:
40:
39:Cell division
33:
19:
3871:
3823:
3800:
3769:
3752:
3730:
3723:Cell potency
3599:
3595:
3585:
3573:. Retrieved
3571:. 2021-04-29
3568:
3559:
3547:. Retrieved
3543:
3534:
3502:(1): 17–26.
3499:
3495:
3485:
3432:
3428:
3414:
3379:
3375:
3327:
3323:
3313:
3272:
3268:
3262:
3227:
3223:
3213:
3178:
3174:
3164:
3131:
3127:
3067:
3063:
3017:
3013:
3007:
2972:
2968:
2958:
2931:
2927:
2917:
2893:(3): 721–9.
2890:
2886:
2876:
2865:. Retrieved
2861:the original
2856:
2847:
2814:
2810:
2756:
2752:
2699:
2695:
2685:
2650:
2646:
2598:
2594:
2526:
2522:
2476:
2472:
2459:
2419:(405): 405.
2416:
2412:
2399:
2364:
2358:
2348:
2344:
2339:
2306:
2302:
2296:
2264:(1): 15–37.
2261:
2257:
2247:
2210:
2204:
2159:
2155:
2145:
2120:
2116:
2103:
2092:. Retrieved
2088:the original
2067:
2063:
2053:
2010:
2006:
1996:
1972:(1): 62–70.
1969:
1965:
1955:
1944:. Retrieved
1940:the original
1919:
1915:
1905:
1880:
1876:
1866:
1811:
1805:
1762:
1758:
1748:
1716:(1): 18–36.
1713:
1709:
1699:
1664:
1660:
1650:
1634:. Springer.
1631:
1625:
1605:
1598:
1577:
1569:
1557:. Retrieved
1547:
1528:
1474:
1470:
1464:
1421:
1417:
1407:
1374:
1370:
1364:
1355:
1311:
1307:
1297:
1232:
1222:
1219:Bangiomorpha
1207:blebbistatin
1203:
1195:
1188:
1165:
1161:
1141:
1131:(TGFs), and
1119:
1108:
1100:
1079:
1049:
1023:DNA sequence
1020:
1004:
991:
966:
931:pluripotency
916:
895:
887:
873:
844:
824:
821:
808:
770:
754:
748:
731:
725:
721:
705:
678:
630:
606:pluripotency
572:
565:
561:cell culture
557:regenerative
539:
518:
506:
502:
445:
432:
423:
415:
395:
390:neurogenesis
383:
371:
347:
340:
305:
278:self-renewal
225:
215:
212:cell potency
209:
181:
123:
122:
3770:Multipotent
3753:Pluripotent
2070:(2): 81–3.
2064:Mol. Interv
1877:Development
1492:2433/159777
1056:euchromatin
854:fibroblasts
736:cytokinesis
639:of all the
602:totipotency
587:osteoblasts
530:liposarcoma
515:vascularity
402:bone marrow
374:multipotent
367:pluripotent
266:multipotent
262:fibroblasts
227:pluripotent
222:blastomeres
168:epigenetics
3889:Categories
3731:Totipotent
3684:Stem cells
3324:J Neurosci
3224:Cancer Res
2867:2016-12-26
2169:1907.09551
2162:: 110031.
2094:2010-12-26
1946:2008-01-01
1559:1 November
1290:References
1217:See also:
1036:nucleosome
1021:While the
956:ectodermal
804:stem cells
793:epigenetic
665:stochastic
617:See also:
613:Mechanisms
591:adipocytes
553:amphibians
526:Micrograph
511:lipoblasts
499:Micrograph
456:asparagine
427:stem cells
425:Epithelial
359:blastocyst
336:chromosome
326:, such as
324:cell types
316:stem cells
308:germ cells
300:See also:
217:totipotent
3801:Unipotent
3645:CC BY 4.0
3626:0960-9822
3459:0027-8424
3175:Genes Dev
2839:205274850
2595:J Exp Med
1856:ignored (
1846:cite book
1438:1552-4469
1314:(1): 67.
1115:β-catenin
1104:epigenome
1076:Stem cell
1011:apoptosis
935:chromatin
801:mammalian
797:cell fate
785:enhancers
633:expresses
575:reversine
410:platelets
274:unipotent
196:epidermis
175:the same
128:stem cell
49:Stem cell
3873:Category
3634:33852871
3569:BBC News
3544:phys.org
3526:19570510
3477:25422450
3406:16109483
3398:16923388
3354:15958744
3305:29965488
3297:15029199
3254:16778178
3148:20944593
3102:22297846
3042:34509771
3034:23085715
2991:15680324
2950:12667453
2909:12667454
2831:20944600
2791:20616255
2726:23333102
2677:21663792
2625:20975044
2561:21289626
2493:25641423
2451:36697417
2331:10915628
2297:Science
2280:14623229
2196:31568790
2137:17291181
2084:15087480
1988:11795984
1838:14594207
1797:26933693
1740:21729779
1691:19763105
1501:16904174
1456:20436487
1391:17377526
1340:26449665
1253:See also
1225:holozoan
1172:H3K27me3
1087:enhancer
891:In vitro
781:promoter
701:enhancer
689:bacteria
583:myotubes
501:showing
484:endoderm
480:mesoderm
476:ectoderm
468:blastula
448:arginine
3604:Bibcode
3517:2768283
3468:4267376
3437:Bibcode
3345:6724881
3277:Bibcode
3245:4386278
3205:9649508
3156:6911946
3093:4144424
3072:Bibcode
2999:7193829
2782:3006433
2761:Bibcode
2753:Science
2717:3563935
2668:5603300
2616:2964577
2552:3100360
2531:Bibcode
2501:2579314
2442:9876972
2421:Bibcode
2391:8408198
2382:2119814
2311:Bibcode
2303:Science
2174:Bibcode
2045:7516873
2036:1519468
2027:3431838
1924:Bibcode
1897:3268408
1788:4771444
1767:Bibcode
1731:3610574
1682:2913577
1509:1565219
1447:2873061
1399:3353748
1331:4599742
1229:protist
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