Maintaining differentiated cellular identity

Nature Reviews Genetics

Volumn 13, Issue 6, 2012, Pages 429-439

  Holmberg, Johan ^a   Perlmann, Thomas ^b  

^a LUDWIG INSTITUTE FOR CANCER RESEARCH   (Sweden)

^b KAROLINSKA INSTITUTE   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

CCAAT ENHANCER BINDING PROTEIN ALPHA; CCAAT ENHANCER BINDING PROTEIN BETA; CRE RECOMBINASE; HEPATOCYTE NUCLEAR FACTOR 3ALPHA; HEPATOCYTE NUCLEAR FACTOR 3BETA; HEPATOCYTE NUCLEAR FACTOR 4ALPHA; NUCLEAR RECEPTOR RELATED FACTOR 1; RAG2 PROTEIN; TESTOSTERONE; TRANSCRIPTION FACTOR FOXP3; TRANSCRIPTION FACTOR PAX5; TRANSCRIPTION FACTOR PITX3; TRANSCRIPTION FACTOR SOX9;

AUTOREGULATION; B LYMPHOCYTE; CAENORHABDITIS ELEGANS; CELL DIFFERENTIATION; CELL FATE; CELL FUNCTION; CELL FUSION; CELL LINEAGE; CELL MATURATION; CELL NUCLEUS; CELL RENEWAL; CELL TRANSDIFFERENTIATION; CYTOPLASM; DNA METHYLATION; DROSOPHILA MELANOGASTER; ENDOTHELIUM CELL; GENE ACTIVATION; GENE EXPRESSION; GENE SILENCING; GENETIC ASSOCIATION; HETEROKARYON; HISTONE MODIFICATION; HUMAN; LEYDIG CELL; LOSS OF FUNCTION MUTATION; MITOSIS; NONHUMAN; NUCLEAR REPROGRAMMING; PANCREAS ISLET BETA CELL; PARKINSON DISEASE; PHENOTYPE; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SCHIZOPHRENIA; SERTOLI CELL; SEX DETERMINATION; SOMATIC CELL; TESTOSTERONE BLOOD LEVEL;

ANIMALS; CELL DEDIFFERENTIATION; CELL DIFFERENTIATION; CELL TRANSDIFFERENTIATION; GENE REGULATORY NETWORKS; HUMANS; INDUCED PLURIPOTENT STEM CELLS; MODELS, GENETIC; PLURIPOTENT STEM CELLS; TRANSCRIPTION FACTORS;

EID: 84862070237     PISSN: 14710056     EISSN: 14710064     Source Type: Journal    
DOI: 10.1038/nrg3209     Document Type: Review

References (139)

1. Spemann, H. Embryonic Development and Induction (Yale Univ. Press, 1938).
2. Gurdon, J. B. The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. J. Embryol. Exp. Morphol. 10, 622-640 (1962).
3. Wilmut, I., Schnieke, A. E., McWhir, J., Kind, A. J. & Campbell, K. H. Viable offspring derived from fetal and adult mammalian cells. Nature 385, 810-813 (1997). (Pubitemid 27106068)
4. Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663-676 (2006). (Pubitemid 44233629)
5. Graf, T. & Enver, T. Forcing cells to change lineages. Nature 462, 587-594 (2009).
6. Hanna, J. H., Saha, K. & Jaenisch, R. Pluripotency and cellular reprogramming: facts, hypotheses, unresolved issues. Cell 143, 508-525 (2010).
7. Yamanaka, S. & Blau, H. M. Nuclear reprogramming to a pluripotent state by three approaches. Nature 465, 704-712 (2010).
8. Eminli, S. et al. Differentiation stage determines potential of hematopoietic cells for reprogramming into induced pluripotent stem cells. Nature Genet. 41, 968-976 (2009).
9. Pasque, V., Jullien, J., Miyamoto, K., Halley-Stott, R. P. & Gurdon, J. B. Epigenetic factors influencing resistance to nuclear reprogramming. Trends Genet. 27, 516-525 (2011).
10. Holmberg, J. et al. Activation of neural and pluripotent stem cell signatures correlates with increased malignancy in human glioma. PLoS ONE 6, e18454 (2011).
11. Ben-Porath, I. et al. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nature Genet. 40, 499-507 (2008). (Pubitemid 351601215)
12. Slack, J. M. W. Metaplasia and transdifferentiation: from pure biology to the clinic. Nature Rev. Mol. Cell Biol. 8, 369-378 (2007). (Pubitemid 46643236)
13. Harris, H. & Watkins, J. F. Hybrid cells derived from mouse and man: artificial heterokaryons of mammalian cells from different species. Nature 205, 640-646 (1965).
14. Bolund, L., Ringertz, N. R. & Harris, H. Changes in the cytochemical properties of erythrocyte nuclei reactivated by cell fusion. J. Cell Sci. 4, 71-87 (1969).
15. Blau, H. M., Chiu, C. P. & Webster, C. Cytoplasmic activation of human nuclear genes in stable heterocaryons. Cell 32, 1171-1180 (1983). (Pubitemid 13033052)
16. Blau, H. M. et al. Plasticity of the differentiated state. Science 230, 758-766 (1985). (Pubitemid 16193964)
17. Wright, W. E. Control of differentiation in heterokaryons and hybrids involving differentiation-defective myoblast variants. J. Cell Biol. 98, 436-443 (1984). (Pubitemid 14196461)
18. Miller, S. C., Pavlath, G. K., Blakely, B. T. & Blau, H. M. Muscle cell components dictate hepatocyte gene expression and the distribution of the Golgi apparatus in heterokaryons. Genes Dev. 2, 330-340 (1988).
19. Palermo, A. et al. Nuclear reprogramming in heterokaryons is rapid, extensive, and bidirectional. FASEB J. 23, 1431-1440 (2009).
20. Terranova, R., Pereira, C. F., Du Roure, C., Merkenschlager, M. & Fisher, A. G. Acquisition and extinction of gene expression programs are separable events in heterokaryon reprogramming. J. Cell Sci. 119, 2065-2072 (2006). (Pubitemid 43904961)
21. Zhang, F., Pomerantz, J. H., Sen, G., Palermo, A. T. & Blau, H. M. Active tissue-specific DNA demethylation conferred by somatic cell nuclei in stable heterokaryons. Proc. Natl Acad. Sci. USA 104, 4395-4400 (2007). (Pubitemid 47186237)
22. Bhutani, N. et al. Reprogramming towards pluripotency requires AID-dependent DNA demethylation. Nature 463, 1042-1047 (2010).
23. Blau, H. M. & Baltimore, D. Differentiation requires continuous regulation. J. Cell Biol. 112, 781-783 (1991). (Pubitemid 21909626)
24. Davis, R. L., Weintraub, H. & Lassar, A. B. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell 51, 987-1000 (1987).
25. Kulessa, H., Frampton, J. & Graf, T. GATA-1 reprograms avian myelomonocytic cell lines into eosinophils, thromboblasts, and erythroblasts. Genes Dev. 9, 1250-1262 (1995).
26. Nerlov, C. & Graf, T. PU.1 induces myeloid lineage commitment in multipotent hematopoietic progenitors. Genes Dev. 12, 2403-2412 (1998). (Pubitemid 28371359)
27. Visvader, J. E., Elefanty, A. G., Strasser, A. & Adams, J. M. GATA-1 but not SCL induces megakaryocytic differentiation in an early myeloid line. EMBO J. 11, 4557-4564 (1992).
28. Seale, P. et al. PRDM16 controls a brown fat/skeletal muscle switch. Nature 454, 961-967 (2008).
29. Briscoe, J. et al. Homeobox gene Nkx2.2 and specification of neuronal identity by graded Sonic hedgehog signalling. Nature 398, 622-627 (1999). (Pubitemid 29183690)
30. Pattyn, A., Hirsch, M., Goridis, C. & Brunet, J. F. Control of hindbrain motor neuron differentiation by the homeobox gene Phox2b. Development 127, 1349-1358 (2000). (Pubitemid 30232587)
31. Simeone, A., Puelles, E. & Acampora, D. The Otx family. Curr. Opin. Genet. Dev. 12, 409-415 (2002). (Pubitemid 34722919)
32. Andersson, E. et al. Identification of intrinsic determinants of midbrain dopamine neurons. Cell 124, 393-405 (2006). (Pubitemid 43121986)
33. Panman, L. et al. Transcription factor-induced lineage selection of stem-cell-derived neural progenitor cells. Cell Stem Cell 8, 663-675 (2011).
34. Alon, U. Network motifs: theory and experimental approaches. Nature Rev. Genet. 8, 450-461 (2007). (Pubitemid 46789247)
35. Davidson, E. H. & Levine, M. S. Properties of developmental gene regulatory networks. Proc. Natl Acad. Sci. USA 105, 20063-20066 (2008).
36. Vierbuchen, T. et al. Direct conversion of fibroblasts to functional neurons by defined factors. Nature 463, 1035-1041 (2010).
37. Caiazzo, M. et al. Direct generation of functional dopaminergic neurons from mouse and human fibroblasts. Nature 476, 224-227 (2011).
38. Ieda, M. et al. Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell 142, 375-386 (2010).
39. Kim, J. et al. Functional integration of dopaminergic neurons directly converted from mouse fibroblasts. Cell Stem Cell 9, 413-419 (2011).
40. Pfisterer, U. et al. Direct conversion of human fibroblasts to dopaminergic neurons. Proc. Natl Acad. Sci. USA 108, 10343-10348 (2011).
41. Sekiya, S. & Suzuki, A. Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors. Nature 475, 390-393 (2011).
42. Feng, R. et al. PU.1 and C/EBPα/β convert fibroblasts into macrophage-like cells. Proc. Natl Acad. Sci. USA 105, 6057-6062 (2008). (Pubitemid 351758398)
43. Zhou, Q., Brown, J., Kanarek, A., Rajagopal, J. & Melton, D. In vivo reprogramming of adult pancreatic exocrine cells to β-cells. Nature 455, 627-632 (2008).
44. Hobert, O. Regulatory logic of neuronal diversity: terminal selector genes and selector motifs. Proc. Natl Acad. Sci. USA 105, 20067-20071 (2008).
45. Chang, S., Johnston, R. J. & Hobert, O. A transcriptional regulatory cascade that controls left/right asymmetry in chemosensory neurons of C. elegans. Genes Dev. 17, 2123-2137 (2003). (Pubitemid 37052292)
46. Etchberger, J. F. et al. The molecular signature and cis-regulatory architecture of a C. elegans gustatory neuron. Genes Dev. 21, 1653-1674 (2007). (Pubitemid 47026369)
47. Uchida, O., Nakano, H., Koga, M. & Ohshima, Y. The C. elegans che-1 gene encodes a zinc finger transcription factor required for specification of the ASE chemosensory neurons. Development 130, 1215-1224 (2003). (Pubitemid 36410771)
48. Altun-Gultekin, Z. et al. A regulatory cascade of three homeobox genes, ceh-10, ttx-3 and ceh-23, controls cell fate specification of a defined interneuron class in C. elegans. Development 128, 1951-1969 (2001). (Pubitemid 32600460)
49. Duggan, A., Ma, C. & Chalfie, M. Regulation of touch receptor differentiation by the Caenorhabditis elegans mec-3 and unc-86 genes. Development 125, 4107-4119 (1998). (Pubitemid 28515448)
50. Wenick, A. S. & Hobert, O. Genomic cis-regulatory architecture and trans-acting regulators of a single interneuron-specific gene battery in C. elegans. Dev. Cell 6, 757-770 (2004). (Pubitemid 38745411)
51. Xue, D., Tu, Y. & Chalfie, M. Cooperative interactions between the Caenorhabditis elegans homeoproteins UNC-86 and MEC-3. Science 261, 1324-1328 (1993). (Pubitemid 24081169)
52. Zhang, Y. et al. Identification of genes expressed in C. elegans touch receptor neurons. Nature 418, 331-335 (2002). (Pubitemid 34790684)
53. Kratsios, P., Stolfi, A., Levine, M. & Hobert, O. Coordinated regulation of cholinergic motor neuron traits through a conserved terminal selector gene. Nature Neurosci. 15, 205-214 (2012).
54. Corbo, J. C. et al. CRX ChIP-seq reveals the cis-regulatory architecture of mouse photoreceptors. Genome Res. 20, 1512-1525 (2010).
55. Flames, N. & Hobert, O. Gene regulatory logic of dopamine neuron differentiation. Nature 458, 885-889 (2009).
56. Wang, S. & Turner, E. E. Expression of dopamine pathway genes in the midbrain is independent of known ETS transcription factor activity. J. Neurosci. 30, 9224-9227 (2010).
57. Smidt, M. P. & Burbach, J. P. H. How to make a mesodiencephalic dopaminergic neuron. Nature Rev. Neurosci. 8, 21-32 (2007). (Pubitemid 46011996)
58. Kadkhodaei, B. et al. Nurr1 is required for maintenance of maturing and adult midbrain dopamine neurons. J. Neurosci. 29, 15923-15932 (2009).
59. Baumgardt, M., Miguel-Aliaga, I., Karlsson, D., Ekman, H. & Thor, S. Specification of neuronal identities by feedforward combinatorial coding. PLoS Biol. 5, e37 (2007).
60. Eade, K. T., Fancher, H. A., Ridyard, M. S. & Allan, D. W. Developmental transcriptional networks are required to maintain neuronal subtype identity in the mature nervous system. PLoS Genet. 8, e1002501 (2012).
61. Metzger, D., & Chambon, P. Site-and time-specific gene targeting in the mouse. Methods 24, 71-80 (2001). (Pubitemid 32846445)
62. Cobaleda, C., Jochum, W. & Busslinger, M. Conversion of mature B cells into T cells by dedifferentiation to uncommitted progenitors. Nature 449, 473-477 (2007). (Pubitemid 47509547)
63. Ghosh, H. S., Cisse, B., Bunin, A., Lewis, K. L. & Reizis, B. Continuous expression of the transcription factor e2-2 maintains the cell fate of mature plasmacytoid dendritic cells. Immunity 33, 905-916 (2010).
64. Johnson, N. C. et al. Lymphatic endothelial cell identity is reversible and its maintenance requires Prox1 activity. Genes Dev. 22, 3282-3291 (2008).
65. Uhlenhaut, N. H. et al. Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation. Cell 139, 1130-1142 (2009).
66. Li, P. et al. Reprogramming of T cells to natural killer-like cells upon Bcl11b deletion. Science 329, 85-89 (2010).
67. Williams, L. M. & Rudensky, A. Y. Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3. Nature Immunol. 8, 277-284 (2007). (Pubitemid 46745377)
68. Wan, Y. Y. & Flavell, R. A. Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression. Nature 445, 766-770 (2007). (Pubitemid 46279706)
69. Matson, C. K. et al. DMRT1 prevents female reprogramming in the postnatal mammalian testis. Nature 476, 101-104 (2011).
70. Nutt, S. L., Heavey, B., Rolink, A. G. & Busslinger, M. Commitment to the B-lymphoid lineage depends on the transcription factor Pax5. Nature 401, 556-562 (1999).
71. Mikkola, I., Heavey, B., Horcher, M. & Busslinger, M. Reversion of B cell commitment upon loss of Pax5 expression. Science 297, 110-113 (2002). (Pubitemid 34743105)
72. McManus, S. et al. The transcription factor Pax5 regulates its target genes by recruiting chromatin-modifying proteins in committed B cells. EMBO J. 30, 2388-2404 (2011).
73. Wigle, J. T. et al. An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype. EMBO J. 21, 1505-1513 (2002). (Pubitemid 34614607)
74. Schmidt, D. et al. The murine winged-helix transcription factor Foxl2 is required for granulosa cell differentiation and ovary maintenance. Development 131, 933-942 (2004). (Pubitemid 38263207)
75. Uda, M. et al. Foxl2 disruption causes mouse ovarian failure by pervasive blockage of follicle development. Hum. Mol. Genet. 13, 1171-1181 (2004). (Pubitemid 38786999)
76. Masuyama, H. et al. Dmrt1 mutation causes a male-to-female sex reversal after the sex determination by Dmy in the medaka. Chromosome Res. 20, 163-176 (2011).
77. Delogu, A. et al. Gene repression by Pax5 in B cells is essential for blood cell homeostasis and is reversed in plasma cells. Immunity 24, 269-281 (2006).
78. Xie, H., Ye, M., Feng, R. & Graf, T. Stepwise reprogramming of B cells into macrophages. Cell 117, 663-676 (2004). (Pubitemid 38692531)
79. Thorel, F. et al. Conversion of adult pancreatic α-cells to β-cells after extreme β-cell loss. Nature 464, 1149-1154 (2010).
80. Cao, Y. et al. Genome-wide MyoD binding in skeletal muscle cells: a potential for broad cellular reprogramming. Dev. Cell 18, 662-674 (2010).
81. Schebesta, A. et al. Transcription factor Pax5 activates the chromatin of key genes involved in B cell signaling, adhesion, migration, and immune function. Immunity 27, 49-63 (2007). (Pubitemid 47096800)
82. Odom, D. T. et al. Control of pancreas and liver gene expression by HNF transcription factors. Science 303, 1378-1381 (2004). (Pubitemid 38269432)
83. Song, N.-N. et al. Adult raphe-specific deletion of lmx1b leads to central serotonin deficiency. PLoS ONE 6, e15998 (2011).
84. Zhao, Z.-Q. et al. Lmx1b is required for maintenance of central serotonergic neurons and mice lacking central serotonergic system exhibit normal locomotor activity. J. Neurosci. 26, 12781-12788 (2006). (Pubitemid 44904573)
85. Hendricks, T., Francis, N., Fyodorov, D. & Deneris, E. S. The ETS domain factor Pet-1 is an early and precise marker of central serotonin neurons and interacts with a conserved element in serotonergic genes. J. Neurosci. 19, 10348-10356 (1999). (Pubitemid 30228042)
86. Cheng, L. et al. Lmx1b, Pet-1, and Nkx2.2 coordinately specify serotonergic neurotransmitter phenotype. J. Neurosci. 23, 9961-9967 (2003). (Pubitemid 37392541)
87. Ding, Y. Q. et al. Lmx1b is essential for the development of serotonergic neurons. Nature Neurosci. 6, 933-938 (2003).
88. Liu, C. et al. Pet-1 is required across different stages of life to regulate serotonergic function. Nature Neurosci. 13, 1190-1198 (2010).
89. Gao, N. et al. Dynamic regulation of Pdx1 enhancers by Foxa1 and Foxa2 is essential for pancreas development. Genes Dev. 22, 3435-3448 (2008).
90. Lee, C. S., Sund, N. J., Behr, R., Herrera, P. L. & Kaestner, K. H. Foxa2 is required for the differentiation of pancreatic α-cells. Dev. Biol. 278, 484-495 (2005). (Pubitemid 40175044)
91. Friedman, J. R. & Kaestner, K. H. The Foxa family of transcription factors in development and metabolism. Cell. Mol. Life Sci. 63, 2317-2328 (2006). (Pubitemid 44653042)
92. Gao, N. et al. Foxa1 and Foxa2 maintain the metabolic and secretory features of the mature β-cell. Mol. Endocrinol. 24, 1594-1604 (2010).
93. Parviz, F. et al. Hepatocyte nuclear factor 4α controls the development of a hepatic epithelium and liver morphogenesis. Nature Genet. 34, 292-296 (2003). (Pubitemid 36792861)
94. Li, J., Ning, G. & Duncan, S. A. Mammalian hepatocyte differentiation requires the transcription factor HNF-4α. Genes Dev. 14, 464-474 (2000). (Pubitemid 30131891)
95. Hayhurst, G. P., Lee, Y. H., Lambert, G., Ward, J. M. & Gonzalez, F. J. Hepatocyte nuclear factor 4α (nuclear receptor 2A1) is essential for maintenance of hepatic gene expression and lipid homeostasis. Mol. Cell. Biol. 21, 1393-1403 (2001). (Pubitemid 32114986)
96. Sund, N. J. et al. Hepatocyte nuclear factor 3β (Foxa2) is dispensable for maintaining the differentiated state of the adult hepatocyte. Mol. Cell. Biol. 20, 5175-5183 (2000). (Pubitemid 30431570)
97. Kyrmizi, I. et al. Plasticity and expanding complexity of the hepatic transcription factor network during liver development. Genes Dev. 20, 2293-2305 (2006).
98. Martinez-Jimenez, C. P., Kyrmizi, I., Cardot, P., Gonzalez, F. J. & Talianidis, I. Hepatocyte nuclear factor 4α coordinates a transcription factor network regulating hepatic fatty acid metabolism. Mol. Cell. Biol. 30, 565-577 (2010).
99. Lewis, E. B. A gene complex controlling segmentation in Drosophila. Nature 276, 565-570 (1978). (Pubitemid 9087758)
100. Busturia, A. & Morata, G. Ectopic expression of homeotic genes caused by the elimination of the Polycomb gene in Drosophila imaginal epidermis. Development 104, 713-720 (1988). (Pubitemid 19028020)
101. Simon, J. A. & Kingston, R. E. Mechanisms of polycomb gene silencing: knowns and unknowns. Nature Rev. Mol. Cell Biol. 10, 697-708 (2009).
102. Ringrose, L. & Paro, R. Epigenetic regulation of cellular memory by the Polycomb and Trithorax group proteins. Annu. Rev. Genet. 38, 413-443 (2004). (Pubitemid 40013734)
103. Beisel, C. & Paro, R. Silencing chromatin: comparing modes and mechanisms. Nature Rev. Genet. 12, 123-135 (2011).
104. Pauli, A., Rinn, J. L. & Schier, A. F. Non-coding RNAs as regulators of embryogenesis. Nature Rev. Genet. 12, 136-149 (2011).
105. Rinn, J. L. et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129, 1311-1323 (2007). (Pubitemid 46962090)
106. Bracken, A. P., Dietrich, N., Pasini, D., Hansen, K. H. & Helin, K. Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions. Genes Dev. 20, 1123-1136 (2006).
107. Pasini, D., Bracken, A. P., Hansen, J. B., Capillo, M. & Helin, K. The Polycomb group protein Suz12 is required for embryonic stem cell differentiation. Mol. Cell. Biol. 27, 3769-3779 (2007). (Pubitemid 46726184)
108. Boyer, L. A. et al. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 441, 349-353 (2006). (Pubitemid 44050199)
109. Ezhkova, E. et al. Ezh2 orchestrates gene expression for the stepwise differentiation of tissue-specific stem cells. Cell 136, 1122-1135 (2009).
110. Lee, T. I. et al. Control of developmental regulators by Polycomb in human embryonic stem cells. Cell 125, 301-313 (2006). (Pubitemid 44313811)
111. Mohn, F. et al. Lineage-specific polycomb targets and de novo DNA methylation define restriction and potential of neuronal progenitors. Mol. Cell 30, 755-766 (2008).
112. Bracken, A. P. & Helin, K. Polycomb group proteins: navigators of lineage pathways led astray in cancer. Nature Rev. Cancer 9, 773-784 (2009).
113. Bantignies, F. & Cavalli, G. Cellular memory and dynamic regulation of polycomb group proteins. Curr. Opin. Cell Biol. 18, 275-283 (2012).
114. Vire, E. et al. The Polycomb group protein EZH2 directly controls DNA methylation. Nature 439, 871-874 (2006). (Pubitemid 43255707)
115. Ohm, J. E. et al. A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing. Nature Genet. 39, 237-242 (2007). (Pubitemid 46184356)
116. Schlesinger, Y. et al. Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer. Nature Genet. 39, 232-236 (2007). (Pubitemid 46184355)
117. Widschwendter, M. et al. Epigenetic stem cell signature in cancer. Nature Genet. 39, 157-158 (2007). (Pubitemid 46184343)
118. Eskeland, R. et al. Ring1B compacts chromatin structure and represses gene expression independent of histone ubiquitination. Mol. Cell 38, 452-464 (2010).
119. Zhang, Y. et al. Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. Genes Dev. 13, 1924-1935 (1999). (Pubitemid 29407360)
120. Pasque, V., Halley-Stott, R. P., Gillich, A., Garrett, N. & Gurdon, J. B. Epigenetic stability of repressed states involving the histone variant macroH2A revealed by nuclear transfer to Xenopus oocytes. Nucleus 2, 533-539 (2011).
121. Bar-Nur, O., Russ, H. A., Efrat, S. & Benvenisty, N. Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet β cells. Cell Stem Cell 9, 17-23 (2011).
122. Zhao, X.-y. et al. iPS cells produce viable mice through tetraploid complementation. Nature 461, 86-90 (2009).
123. Kim, K. et al. Epigenetic memory in induced pluripotent stem cells. Nature 467, 285-290 (2010).
124. Polo, J. M. et al. Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells. Nature Biotech. 28, 848-855 (2010).
125. Lister, R. et al. Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature 471, 68-73 (2011).
126. Epsztejn-Litman, S. et al. De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes. Nature Struct. Mol. Biol. 15, 1176-1183 (2008).
127. Payer, B., Lee, J. T. & Namekawa, S. H. X-inactivation and X-reactivation: epigenetic hallmarks of mammalian reproduction and pluripotent stem cells. Hum. Genet. 130, 265-280 (2011).
128. Payer, B. & Lee, J. T. X chromosome dosage compensation: how mammals keep the balance. Annu. Rev. Genet. 42, 733-772 (2008).
129. Mullighan, C. G. et al. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature 446, 758-764 (2007). (Pubitemid 46582031)
130. Balandina, A., Lecart, S., Dartevelle, P., Saoudi, A. & Berrih-Aknin, S. Functional defect of regulatory CD4+CD25+ T cells in the thymus of patients with autoimmune myasthenia gravis. Blood 105, 735-741 (2005). (Pubitemid 40070760)
131. Miura, Y. et al. Association of Foxp3 regulatory gene expression with graft-versus-host disease. Blood 104, 2187-2193 (2004). (Pubitemid 39297878)
132. Liu, Q. et al. Neuronal LRP1 knockout in adult mice leads to impaired brain lipid metabolism and progressive, age-dependent synapse loss and neurodegeneration. J. Neurosci. 30, 17068-17078 (2010).
133. Bergman, O., Westberg, L., Nilsson, L. G., Adolfsson, R. & Eriksson, E. Preliminary evidence that polymorphisms in dopamine-related transcription factors LMX1A, LMX1B and PITX3 are associated with schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry 34, 1094-1097 (2010).
134. Le, W. D. et al. Mutations in NR4A2 associated with familial Parkinson disease. Nature Genet. 33, 85-89 (2003).
135. Herrup, K. & Yang, Y. Cell cycle regulation in the postmitotic neuron: oxymoron or new biology? Nature Rev. Neurosci. 8, 368-378 (2007). (Pubitemid 46652467)
136. Nicolay, B. N., Bayarmagnai, B., Moon, N. S., Benevolenskaya, E. V. & Frolov, M. V. Combined inactivation of pRB and hippo pathways induces dedifferentiation in the Drosophila retina. PLoS Genet. 6, e1000918 (2010).
137. Ajioka, I. et al. Differentiated horizontal interneurons clonally expand to form metastatic retinoblastoma in mice. Cell 131, 378-390 (2007). (Pubitemid 47576143)
138. Eade, K. T., & Allan, D. W. Neuronal phenotype in the mature nervous system is maintained by persistent retrograde bone morphogenetic protein signaling. J. Neurosci. 29, 3852-3864 (2009).
139. Lσpez-Coviella, I. Induction and maintenance of the neuronal cholinergic phenotype in the central nervous system by BMP-9. Science 289, 313-316 (2000). (Pubitemid 30469912)