X-chromosome inactivation in Rett syndrome human induced pluripotent stem cells

Frontiers in Psychiatry

Volumn 3, Issue MAR, 2012, Pages

  Cheung, Aaron Y L ^a,b   Horvath, Lindsay M ^c   Carrel, Laura ^c   Ellis, James ^a,b  

^a HOSPITAL FOR SICK CHILDREN   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

^c PENN STATE COLLEGE OF MEDICINE   (United States)

Author keywords

Human induced pluripotent stem cells; Rett syndrome; X chromosome inactivation

Indexed keywords

3 DEAZANEPLANOCIN A; ANDROGEN RECEPTOR; BUTYRIC ACID; FORSKOLIN; HISTONE H3; KRUPPEL LIKE FACTOR 2; KRUPPEL LIKE FACTOR 4; METHYL CPG BINDING PROTEIN 2; MYC PROTEIN; OCTAMER TRANSCRIPTION FACTOR 4; TELOMERASE REVERSE TRANSCRIPTASE; TRANSCRIPTION FACTOR EZH2; TRANSCRIPTION FACTOR NANOG; TRANSCRIPTION FACTOR SOX2; UNCLASSIFIED DRUG; UNTRANSLATED RNA; XIST RNA;

ALPHA THALASSEMIA; CDKL 5 GENE; CELL ASSAY; CELL DIFFERENTIATION; CELL ISOLATION; CELL TRANSFORMATION; CHROMOSOME ANALYSIS; CHROMOSOME LOSS; CHROMOSOME MARKER; CHROMOSOMES AND CHROMOSOMAL PHENOMENA; COFFIN LOWRY SYNDROME; DOWN REGULATION; DYSTROPHINOPATHY; EMBRYONIC STEM CELL; FLUORESCENCE IN SITU HYBRIDIZATION; FRAGILE X SYNDROME; GENE ACTIVATION; GENE EXPRESSION; HISTONE METHYLATION; HUMAN; HUMAN EMBRYONIC STEM CELL; HUMAN PLURIPOTENT STEM CELL; IMMUNOFLUORESCENCE; IN VITRO STUDY; IN VIVO STUDY; LESCH NYHAN SYNDROME; METHYL CPG BINDING PROTEIN 2 GENE; MICROARRAY ANALYSIS; MUTATIONAL ANALYSIS; NONHUMAN; PLURIPOTENT STEM CELL; PROTEIN DETERMINATION; RETT SYNDROME; RETT SYNDROME HUMAN INDUCED PLURIPOTENT STEM CELL; REVIEW; RNA ANALYSIS; STEM CELL; TELOMERASE REVERSE TRANSCRIPTASE GENE; UPREGULATION; WISKOTT ALDRICH SYNDROME; X CHROMOSOME INACTIVATION; X CHROMOSOME LINKAGE; X CHROMOSOME REACTIVATION;

EID: 84864961375     PISSN: None     EISSN: 16640640     Source Type: Journal    
DOI: 10.3389/fpsyt.2012.00024     Document Type: Review

References (139)

1. Adewumi, O., Aflatoonian, B., Ahrlund-Richter, L., Amit, M., Andrews, P. W., Beighton, G., Bello, P. A., Benvenisty, N., Berry, L. S., Bevan, S., Blum, B., Brooking, J., Chen, K. G., Choo, A. B., Churchill, G. A., Corbel, M., Damjanov, I., Draper, J. S., Dvorak, P., Emanuelsson, K., Fleck, R. A., Ford, A., Gertow, K., Gertsenstein, M., Gokhale, P. J., Hamilton, R. S., Hampl, A., Healy, L. E., Hovatta, O., Hyllner, J., Imreh, M. P., Itskovitz-Eldor, J., Jackson, J., Johnson, J. L., Jones, M., Kee, K., King, B. L., Knowles, B. B., Lako, M., Lebrin, F., Mallon, B. S., Manning, D., Mayshar, Y., McKay, R. D., Michalska, A. E., Mikkola, M., Mileikovsky, M., Minger, S. L., Moore, H. D., Mummery, C. L., Nagy, A., Nakatsuji, N., O'Brien, C. M., Oh, S. K., Olsson, C., Otonkoski, T., Park, K. Y., Passier, R., Patel, H., Patel, M., Pedersen, R., Pera, M. F., Piekarczyk, M. S., Pera, R. A., Reubinoff, B. E., Robins, A. J., Rossant, J., Rugg-Gunn, P., Schulz, T. C., Semb, H., Sherrer, E. S., Siemen, H., Stacey, G. N., Stojkovic, M., Suemori, H., Szatkiewicz, J., Turetsky, T., Tuuri, T., van den Brink, S., Vintersten, K., Vuoristo, S., Ward, D., Weaver, T. A., Young, L. A., and Zhang, W. (2007). Characterization of human embryonic stem cell lines by the International Stem Cell Initiative. Nat. Biotechnol. 25, 803-816.
2. Allen, R. C., Zoghbi, H. Y., Moseley, A. B., Rosenblatt, H. M., and Belmont, J. W. (1992). Methylation of HpaII and HhaI sites near the polymorphic CAG repeatinthe human androgenreceptor gene correlates with X chromosome inactivation. Am. J. Hum. Genet. 51, 1229-1239.
3. Amenduni, M., De Filippis, R., Cheung, A. Y., Disciglio, V., Epistolato, M. C., Ariani, F., Mari, F., Mencarelli, M. A., Hayek,Y., Renieri,A., Ellis, J., and Meloni, I. (2011). iPS cells to model CDKL5-related disorders. Eur. J. Hum. Genet. 19, 1246-1255.
4. Amir, R. E., Van den Veyver, I. B., Wan, M., Tran, C. Q., Francke, U., and Zoghbi, H. Y. (1999). Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat. Genet. 23, 185-188.
5. Ananiev, G., Williams, E. C., Li, H., and Chang, Q. (2011). Isogenic pairs of wild type and mutant induced pluripotent stem cell (iPSC) lines from Rett syndrome patients as in vitro disease model. PLoS ONE 6, e25255. doi:10.1371/journal.pone.0025255.
6. Anokye-Danso, F., Trivedi, C. M., Juhr, D., Gupta, M., Cui, Z., Tian, Y., Zhang, Y., Yang, W., Gruber, P. J., Epstein, J. A., and Morrisey, E. E. (2011). Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell 8, 376-388.
7. Archer, H., Evans, J., Leonard, H., Colvin, L., Ravine, D., Christodoulou, J., Williamson, S., Charman, T., Bailey, M. E., Sampson, J., de Klerk, N., and Clarke, A. (2007). Correlation between clinical severity in patients with Rett syndrome with a p.R168X or p.T158M MECP2 mutation, and the direction and degree of skewing of X-chromosome inactivation. J. Med. Genet. 44, 148-152.
8. Ariani, F., Hayek, G., Rondinella, D., Artuso, R., Mencarelli, M. A., Spanhol-Rosseto, A., Pollazzon, M., Buoni, S., Spiga, O., Ricciardi, S., Meloni, I., Longo, I., Mari, F., Broccoli, V., Zappella, M., and Renieri, A. (2008). FOXG1 is responsible for the congenital variant of Rett syndrome. Am. J. Hum. Genet. 83, 89-93.
9. Augui,S., Filion,G. J., Huart, S., Nora, E., Guggiari, M., Maresca, M., Stewart, A. F., and Heard, E. (2007). Sensing X chromosome pairs before X inactivation via a novel X-pairing region of the Xic. Science 318, 1632-1636.
10. Ballas, N., Lioy, D. T., Grunseich, C., and Mandel, G. (2009). Noncell autonomous influence of MeCP2-deficient glia on neuronal dendritic morphology. Nat. Neurosci.12, 311-317.
11. Barakat, T. S., Gunhanlar, N., Pardo, C. G., Achame, E. M., Ghazvini, M., Boers, R., Kenter, A., Rentmeester, E., Grootegoed, J. A., and Gribnau, J. (2011). RNF12 activates Xist and is essential for X chromosome inactivation. PLoS Genet. 7, e1002001. doi:10.1371/journal.pgen.1002001.
12. Barr, M. L., and Bertram, E. G. (1949). A morphological distinction between neurones of the male and female, and the behaviour of the nucleolar satellite during accelerated nucleoprotein synthesis. Nature 163, 676.
13. Bauman, M. L., Kemper, T. L., and Arin, D. M. (1995). Pervasive neuroanatomic abnormalities of the brain in three cases of Rett's syndrome. Neurology 45, 1581-1586.
14. Ben-Shachar, S., Chahrour, M., Thaller, C., Shaw, C. A., and Zoghbi, H. Y. (2009). Mouse models of MeCP2 disorders share gene expression changes in the cerebellum and hypothalamus. Hum. Mol. Genet. 18, 2431-2442.
15. Brockdorff, N., Ashworth, A., Kay, G. F., Cooper, P., Smith, S., McCabe, V. M., Norris, D. P., Penny, G. D., Patel, D., and Rastan,S. (1991). Conservation of position and exclusive expression of mouse Xist from the inactive X chromosome. Nature 351, 329-331.
16. Brons, I. G., Smithers, L. E., Trotter, M. W., Rugg-Gunn, P., Sun, B., Chuva de Sousa Lopes, S. M., Howlett, S. K., Clarkson, A., Ahrlund-Richter, L., Pedersen, R. A., and Vallier, L. (2007). Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature 448, 191-195.
17. Brown, C. J., Ballabio, A., Rupert, J. L., Lafreniere, R. G., Grompe, M., Tonlorenzi, R., and Willard, H. F. (1991). A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature 349, 38-44.
18. Brown, C. J., Hendrich, B. D., Rupert, J. L., Lafreniere, R. G., Xing, Y., Lawrence, J., and Willard, H. F. (1992). The human XIST gene: analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus. Cell 71, 527-542.
19. Bruck, T., and Benvenisty, N. (2011). Metaanalysis of the heterogeneity of X chromosome inactivation in human pluripotent stem cells. Stem Cell Res 6, 187-193.
20. Buecker, C., Chen, H. H., Polo, J. M., Daheron, L., Bu, L., Barakat, T. S., Okwieka, P., Porter, A., Gribnau, J., Hochedlinger, K., and Geijsen, N. (2010). A murine ESC-like state facilitates transgenesis and homologous recombination in human pluripotent stem cells. Cell Stem Cell 6, 535-546.
21. Chahrour, M., Jung, S. Y., Shaw, C., Zhou, X., Wong, S. T., Qin, J., and Zoghbi, H. Y. (2008). MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 320, 1224-1229.
22. Chahrour, M., and Zoghbi, H. Y. (2007). The story of Rett syndrome: from clinic to neurobiology. Neuron 56, 422-437.
23. Chen, R. Z., Akbarian, S., Tudor, M., and Jaenisch, R. (2001). Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rettlike phenotype in mice. Nat. Genet. 27, 327-331.
24. Cheung, A. Y., Horvath, L. M., Grafodatskaya, D., Pasceri, P., Weksberg, R., Hotta, A., Carrel, L., and Ellis, J. (2011). Isolation of MECP2-null Rett syndrome patient hiPS cells and isogenic controls through X-chromosome inactivation. Hum. Mol. Genet. 20, 2103-2115.
25. Chow, J. C., Ciaudo, C., Fazzari, M. J., Mise, N., Servant, N., Glass, J. L., Attreed, M., Avner, P., Wutz, A., Barillot, E., Greally, J. M., Voinnet, O., and Heard, E. (2010). LINE-1 activity in facultative heterochromatin formation during X chromosome inactivation. Cell 141, 956-969.
26. Chureau, C., Prissette, M., Bourdet, A., Barbe, V., Cattolico, L., Jones, L., Eggen, A., Avner, P., and Duret, L. (2002). Comparative sequence analysis of the X-inactivation center region in mouse, human, and bovine. Genome Res.12, 894-908.
27. Clemson, C. M., McNeil, J. A., Willard, H. F., and Lawrence, J. B. (1996). XIST RNA paints the inactive X chromosome at interphase: evidence for a novel RNA involved in nuclear/chromosome structure. J. Cell Biol 132,259-275.
28. Costanzi, C, and Pehrson, J. R. (1998). Histone macroH2A1 is concentrated in the inactive X chromosome of female mammals. Nature 393, 599-601.
29. Csankovszki, G., Nagy, A., and Jaenisch, R. (2001). Synergism of Xist RNA, DNA methylation, and histone hypoacetylation in maintaining X chromosome inactivation. J. Cell Biol. 153, 773-784.
30. de Napoles, M., Mermoud, J. E., Wakao, R., Tang, Y. A., Endoh, M., Appanah, R., Nesterova, T. B., Silva, J., Otte, A. P., Vidal, M., Koseki, H., and Brockdorff, N. (2004). Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation. Dev. Cell 7, 663-676.
31. Debrand, E., Chureau, C, Arnaud, D., Avner, P., and Heard, E. (1999). Functional analysis of the DXPas34 locus, a 3' regulator of Xist expression. Mol Cell Biol 19, 8513-8525.
32. Dhara, S. K., and Benvenisty, N. (2004). Gene trap as atool for genome annotation and analysis of X chromosome inactivation in human embryonic stem cells. Nucleic Acids Res. 32, 3995-4002.
33. Diaz Perez, S. V., Kim, R., Li, Z., Marquez, V. E., Patel, S., Plath, K., and Clark, A. T. (2012). Derivation of new human embryonic stem cell lines reveals rapid epigenetic progression in vitro that can be prevented by chemical modification of chromatin. Hum. Mol. Genet. 21, 751-764.
34. Donohoe, M. E., Silva, S. S., Pinter, S. F., Xu, N., and Lee, J. T. (2009). The pluripotency factor Oct4 interacts with Ctcf and also controls X-chromosome pairing and counting. Nature 460, 128-132.
35. Dvash, T., Lavon, N., and Fan, G. (2010). Variations of X chromosome inactivation occur in early passages of female human embryonic stem cells. PLoS ONE 5, e11330. doi: 10.1371/journal.pone.0011330.
36. Enver, T., Soneji, S., Joshi, C., Brown, J., Iborra, F., Orntoft, T., Thykjaer, T., Maltby, E., Smith, K., Abu Dawud, R., Jones, M., Matin, M., Gokhale, P., Draper, J., and Andrews, P. W. (2005). Cellular differentiation hierarchies in normal and cultureadapted human embryonic stem cells. Hum. Mol. Genet. 14, 3129-3140.
37. Escamilla-Del-Arenal, M., da Rocha, S. T., and Heard, E. (2011). Evolutionary diversity and developmental regulation of X-chromosome inactivation. Hum. Genet. 130, 307-327.
38. Evans, M. J., and Kaufman, M. H. (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature 292, 154-156.
39. Fan, G., and Tran, J. (2011). X chromosome inactivation in human and mouse pluripotent stem cells. Hum. Genet. 130, 217-222.
40. Fiskus, W., Wang, Y., Sreekumar, A., Buckley, K. M., Shi, H., Jillella, A., Ustun, C., Rao, R., Fernandez, P., Chen, J., Balusu, R., Koul, S., Atadja, P., Marquez, V. E., and Bhalla, K. N. (2009). Combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A and the histone deacetylase inhibitor panobinostat against human AML cells. Blood 114, 2733-2743.
41. Gecz, J., Shoubridge, C., and Corbett, M. (2009). The genetic landscape of intellectual disability arising from chromosome X. Trends Genet. 25, 308-316.
42. Gore, A., Li, Z., Fung, H. L., Young, J. E.,Agarwal,S.,Antosiewicz-Bourget, J., Canto, I., Giorgetti, A., Israel, M. A., Kiskinis, E., Lee, J. H., Loh, Y. H., Manos, P. D., Montserrat, N., Panopoulos, A. D., Ruiz, S., Wilbert, M. L., Yu, J., Kirkness, E. F., Izpisua Belmonte, J. C., Rossi, D. J., Thomson, J. A., Eggan, K., Daley, G. Q., Goldstein, L. S., and Zhang, K. (2011). Somatic coding mutations in human induced pluripotent stem cells. Nature 471, 63-67.
43. Guo, G., Yang, J., Nichols, J., Hall, J. S., Eyres, I., Mansfield, W., and Smith, A. (2009). Klf4 reverts developmentally programmed restriction of ground state pluripotency. Development 136, 1063-1069.
44. Hagberg, B., Aicardi, J., Dias, K., and Ramos, O. (1983). A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett's syndrome: report of 35 cases. Ann. Neurol. 14, 471-479.
45. Hall, L. L., Byron, M., Butler, J., Becker, K. A., Nelson, A., Amit, M., Itskovitz-Eldor, J., Stein, J., Stein, G., Ware, C., and Lawrence, J. B. (2008). X-inactivation reveals epigenetic anomalies in most hESC but identifies sublines that initiate as expected. J. Cell. Physiol. 216, 445-452.
46. Han, S. S., Williams, L. A., and Eggan, K. C. (2011). Constructing and deconstructing stem cell models of neurological disease. Neuron 70, 626-644.
47. Hanna, J., Cheng, A. W., Saha, K., Kim, J., Lengner, C. J., Soldner, F., Cassady, J. P., Muffat, J., Carey, B. W., and Jaenisch, R. (2010). Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs. Proc. Natl. Acad. Sci. U.S.A. 107, 9222-9227.
48. Hansen, D. V., Rubenstein, J. L., and Kriegstein, A. R. (2011). Deriving excitatory neurons of the neocortex from pluripotent stem cells. Neuron 70, 645-660.
49. Hellman, A., and Chess, A. (2007). Gene bodyspecific methylation on the active X chromosome. Science 315, 1141-1143.
50. Hoffman, E. P., Brown, R. H. Jr., and Kunkel, L. M. (1987). Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 51, 919-928.
51. Hoffman, L. M., Hall, L., Batten, J. L., Young, H., Pardasani, D., Baetge, E. E., Lawrence, J., and Carpenter, M. K. (2005). X-inactivation status varies in human embryonic stem cell lines. Stem Cells 23, 1468-1478.
52. Hotta, A., Cheung, A. Y., Farra, N., Vijayaragavan, K., Seguin, C. A., Draper, J. S., Pasceri, P., Maksakova, I. A., Mager, D. L., Rossant, J., Bhatia, M., and Ellis, J. (2009). Isolation of human iPS cells using EOS lentiviral vectors to select for pluripotency. Nat. Methods 6, 370-376.
53. Hu, B. Y., Weick, J. P., Yu, J., Ma, L. X., Zhang, X. Q., Thomson, J. A., and Zhang, S. C. (2010). Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency. Proc. Natl. Acad. Sci. U.S.A. 107, 4335-4340.
54. Hussein, S. M., Batada, N. N., Vuoristo, S., Ching, R. W., Autio, R., Narva, E., Ng, S., Sourour, M., Hamalainen, R., Olsson, C., Lundin, K., Mikkola, M., Trokovic, R., Peitz, M., Brustle, O., Bazett-Jones, D. P., Alitalo, K., Lahesmaa, R., Nagy, A., and Otonkoski, T. (2011). Copy number variation and selection during reprogramming to pluripotency. Nature 471, 58-62.
55. James, D., Levine, A. J., Besser, D., and Hemmati-Brivanlou, A. (2005). TGFbeta/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells. Development 132, 1273-1282.
56. Keohane, A. M., O'Neill L, P., Belyaev, N. D., Lavender, J. S., and Turner, B. M. (1996). X-inactivation and histone H4 acetylation in embryonic stem cells. Dev. Biol. 180, 618-630.
57. Kim, D., Kim, C. H., Moon, J. I., Chung, Y. G., Chang, M. Y., Han, B. S., Ko, S., Yang, E., Cha, K. Y., Lanza, R., and Kim, K. S. (2009). Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 4, 472-476.
58. Kim, K. Y., Hysolli, E., and Park, I. H. (2011). Neuronal maturation defect in induced pluripotent stem cells from patients with Rett syndrome. Proc. Natl. Acad. Sci. U.S.A. 108, 14169-14174.
59. Kishi, N., and Macklis, J. D. (2004). MECP2 is progressively expressed in postmigratory neurons and is involved in neuronal maturation rather than cell fate decisions. Mol. Cell. Neurosci. 27, 306-321.
60. Kohlmaier, A., Savarese, F., Lachner, M., Martens, J., Jenuwein, T., and Wutz, A. (2004). A chromosomal memory triggered by Xist regulates histone methylation in X inactivation. PLoS Biol. 2, E171. doi:10.1371/journal.pbio.0020171.
61. Kunath, T., Saba-El-Leil, M. K., Almousailleakh, M., Wray, J., Meloche, S., and Smith, A. (2007). FGF stimulation of the Erk1/2 signalling cascade triggers transition of pluripotent embryonic stem cells from selfrenewal to lineage commitment. Development 134, 2895-2902.
62. Laurent, L. C., Ulitsky, I., Slavin, I., Tran, H., Schork, A., Morey, R., Lynch, C., Harness, J. V., Lee, S., Barrero, M. J., Ku, S., Martynova, M., Semechkin, R., Galat, V., Gottesfeld, J., Izpisua Belmonte, J. C., Murry, C., Keirstead, H. S., Park,H. S.,Schmidt,U., Laslett, A. L., Muller, F. J., Nievergelt, C. M., Shamir, R., and Loring, J. F. (2011). Dynamic changes in the copy number of pluripotency and cell proliferation genes in human ESCs and iPSCs during reprogramming and time in culture. Cell Stem Cell 8, 106-118.
63. Lee, J. T., Davidow, L. S., and Warshawsky, D. (1999). Tsix, a gene antisense to Xist at the X-inactivation centre. Nat. Genet. 21, 400-404.
64. Lengner, C. J., Gimelbrant, A. A., Erwin, J. A., Cheng, A. W., Guenther, M. G., Welstead, G. G., Alagappan, R., Frampton, G. M., Xu, P., Muffat, J., Santagata, S., Powers, D., Barrett, C. B., Young, R. A., Lee, J. T., Jaenisch, R., and Mitalipova, M. (2010). Derivation of pre-X inactivation human embryonic stem cells under physiological oxygen concentrations. Cell 141, 872-883.
65. Lioy, D. T., Garg, S. K., Monaghan, C. E., Raber, J., Foust, K. D., Kaspar, B. K., Hirrlinger, P. G., Kirchhoff, F., Bissonnette, J. M., Ballas, N., and Mandel, G. (2011). A role for glia in the progression of Rett's syndrome. Nature 475, 497-500.
66. Lister, R., Pelizzola, M., Kida, Y. S., Hawkins, R. D., Nery, J. R., Hon, G., Antosiewicz-Bourget, J., O'Malley, R., Castanon, R., Klugman, S., Downes, M., Yu, R., Stewart, R., Ren, B., Thomson, J. A., Evans, R. M., and Ecker, J. R. (2011). Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature 471, 68-73.
67. Liu, W., and Sun, X. (2009). Skewed X chromosome inactivation in diploid and triploid female human embryonic stem cells. Hum. Reprod. 24, 1834-1843.
68. Ludwig, T. E., Bergendahl, V., Levenstein, M. E., Yu, J., Probasco, M. D., and Thomson, J. A. (2006). Feederindependent culture of human embryonic stem cells. Nat. Methods 3, 637-646.
69. Maezawa, I., and Jin, L. W. (2010). Rett syndrome microglia damage dendrites and synapses by the elevated release of glutamate. J. Neurosci. 30, 5346-5356.
70. Maezawa, I., Swanberg, S., Harvey, D., LaSalle, J. M., and Jin, L. W. (2009). Rett syndrome astrocytes are abnormal and spread MeCP2 deficiency through gap junctions. J. Neurosci. 29, 5051-5061.
71. Maherali, N., Sridharan, R., Xie, W., Utikal, J., Eminli, S., Arnold, K., Stadtfeld, M., Yachechko, R., Tchieu, J., Jaenisch, R., Plath, K., and Hochedlinger, K. (2007). Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell 1, 55-70.
72. Mak, W., Nesterova, T. B., de Napoles, M., Appanah, R., Yamanaka, S., Otte, A. P., and Brockdorff, N. (2004). Reactivation of the paternal X chromosome in early mouse embryos. Science 303, 666-669.
73. Marchetto, M. C., Brennand, K. J., Boyer, L., and Gage, F. H. (2011). Induced pluripotent stem cells (iPSC) and neurologic disease modeling: progress and promises. Hum. Mol. Genet. 20, R109-R115.
74. Marchetto, M. C., Carromeu, C., Acab, A., Yu, D., Yeo, G. W., Mu, Y., Chen, G., Gage, F. H., and Muotri, A. R. (2010). A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell 143, 527-539.
75. Marks, H., Chow, J. C., Denissov, S., Francoijs, K. J., Brockdorff, N., Heard, E., and Stunnenberg, H. G. (2009). Highresolution analysis of epigenetic changes associated with X inactivation. Genome Res. 19, 1361-1373.
76. Martin, G. R. (1981). Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc. Natl. Acad. Sci. U.S.A. 78, 7634-7638.
77. Matsuda, T., Nakamura, T., Nakao, K., Arai, T., Katsuki, M., Heike, T., and Yokota, T. (1999). STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells. EMBO J. 18, 4261-4269.
78. Mayshar, Y., Ben-David, U., Lavon, N., Biancotti, J. C., Yakir, B., Clark, A. T., Plath, K., Lowry, W. E., and Benvenisty, N. (2010). Identification and classification of chromosomal aberrations in human induced pluripotent stem cells. Cell Stem Cell 7, 521-531.
79. Migeon, B. R., Lee, C. H., Chowdhury, A. K., and Carpenter, H. (2002). Species differences in TSIX/Tsix reveal the roles of these genes in X-chromosome inactivation. Am. J. Hum. Genet. 71, 286-293.
80. Minkovsky, A., Patel, S., and Plath, K. (2012). Pluripotency and the transcriptional inactivation of the female mammalian X chromosome. Stem Cells 30, 48-54.
81. Miyoshi, N., Ishii, H., Nagano, H., Haraguchi, N., Dewi, D. L., Kano, Y., Nishikawa, S., Tanemura, M., Mimori, K., Tanaka, F., Saito, T., Nishimura, J., Takemasa, I., Mizushima, T., Ikeda, M., Yamamoto, H., Sekimoto, M., Doki, Y., and Mori, M. (2011). Reprogramming of mouse and human cells to pluripotency using mature microRNAs. Cell Stem Cell 8, 633-638.
82. Murry, C. E., and Keller, G. (2008). Differentiation of embryonic stem cells to clinically relevant populations: lessons from embryonic development. Cell 132, 661-680.
83. Musch, T., Oz, Y., Lyko, F., and Breiling, A. (2010). Nucleoside drugs induce cellular differentiation by caspasedependent degradation of stem cell factors. PLoS ONE 5, e10726. doi:10.1371/journal.pone.0010726.
84. Nan, X., Campoy, F. J., and Bird, A. (1997). MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin. Cell 88, 471-481.
85. Nan, X., Meehan, R. R., and Bird, A. (1993). Dissection of the methyl-CpG binding domain from the chromosomal protein MeCP2. Nucleic Acids Res. 21, 4886-4892.
86. Nan, X., Ng, H. H., Johnson, C. A., Laherty, C. D., Turner, B. M., Eisenman, R. N., and Bird, A. (1998). Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 393, 386-389.
87. Nichols, J., and Smith, A. (2009). Naive and primed pluripotent states. Cell Stem Cell 4, 487-492.
88. Niwa, H., Burdon, T., Chambers, I., and Smith, A. (1998). Selfrenewal of pluripotent embryonic stem cells is mediated via activation of STAT3. Genes Dev. 12, 2048-2060.
89. Ogawa, Y., and Lee, J. T. (2003). Xite, X-inactivation intergenic transcription elements that regulate the probability of choice. Mol. Cell 11, 731-743.
90. Okamoto, I., Otte, A. P., Allis, C. D., Reinberg, D., and Heard, E. (2004). Epigenetic dynamics of imprinted X inactivation during early mouse development. Science 303, 644-649.
91. Okamoto, I., Patrat, C., Thepot, D., Peynot, N., Fauque, P., Daniel, N., Diabangouaya, P., Wolf, J. P., Renard, J. P., Duranthon, V., and Heard, E. (2011). Eutherian mammals use diverse strategies to initiate X-chromosome inactivation during development. Nature 472, 370-374.
92. Osafune, K., Caron, L., Borowiak, M., Martinez, R. J., Fitz-Gerald, C. S., Sato, Y., Cowan, C. A., Chien, K. R., and Melton, D. A. (2008). Marked differences in differentiation propensity among human embryonic stem cell lines. Nat. Biotechnol. 26, 313-315.
93. Park, I. H., Zhao, R., West, J. A., Yabuuchi, A., Huo, H., Ince, T. A., Lerou, P. H., Lensch, M. W., and Daley, G. Q. (2008). Reprogramming of human somatic cells to pluripotency with defined factors. Nature 451, 141-146.
94. Penny, G. D., Kay, G. F., Sheardown, S. A., Rastan, S., and Brockdorff, N. (1996). Requirement for Xist in X chromosome inactivation. Nature 379, 131-137.
95. Percy,A. K., Lane, J. B., Childers, J., Skinner, S., Annese, F., Barrish, J., Caeg, E., Glaze, D. G., and MacLeod, P. (2007). Rett syndrome: North American database. J. Child Neurol. 22, 1338-1341.
96. Plath, K., Fang, J., Mlynarczyk-Evans, S. K., Cao, R., Worringer, K. A., Wang, H., de la Cruz, C. C., Otte, A. P., Panning, B., and Zhang, Y. (2003). Role of histone H3 lysine 27 methylation in X inactivation. Science 300, 131-135.
97. Pomp, O., Dreesen, O., Leong, D. F., Meller-Pomp, O., Tan, T. T., Zhou, F., and Colman, A. (2011). Unexpected X chromosome skewing during culture and reprogramming of human somatic cells can be alleviated by exogenous telomerase. Cell Stem Cell 9, 156-165.
98. Rastan, S. (1982). Timing of X-chromosome inactivation in postimplantation mouse embryos. J. Embryol. Exp. Morphol. 71, 11-24.
99. Reubinoff, B. E., Pera, M. F., Fong, C. Y., Trounson, A., and Bongso, A. (2000). Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nat. Biotechnol. 18, 399-404.
100. Ross, P. J., and Ellis, J. (2010). Modeling complex neuropsychiatric disease with induced pluripotent stem cells. F1000 Biol. Rep. 2, 84.
101. Rossant, J. (2008). Stem cells and early lineage development. Cell 132, 527-531.
102. Saha, K., and Jaenisch, R. (2009). Technical challenges in using human induced pluripotent stem cells to model disease. Cell Stem Cell 5, 584-595.
103. Scala, E., Ariani, F., Mari, F., Caselli, R., Pescucci, C., Longo, I., Meloni, I., Giachino, D., Bruttini, M., Hayek, G., Zappella, M., and Renieri, A. (2005). CDKL5/STK9 is mutated in Rett syndrome variant with infantile spasms. J. Med. Genet. 42, 103-107.
104. Seki, T., Yuasa, S., Oda, M., Egashira, T., Yae, K., Kusumoto, D., Nakata, H., Tohyama, S., Hashimoto, H., Kodaira, M., Okada, Y., Seimiya, H., Fusaki, N., Hasegawa, M., and Fukuda, K. (2010). Generation of induced pluripotent stem cells from human terminally differentiated circulating T cells. Cell Stem Cell 7, 11-14.
105. Sharp, A. J., Stathaki, E., Migliavacca, E., Brahmachary, M., Montgomery, S. B., Dupre, Y., and Antonarakis, S. E. (2011). DNA methylation profiles of human active and inactive X chromosomes. Genome Res. 21, 1592-1600.
106. Shen, Y., Matsuno, Y., Fouse, S. D., Rao, N., Root, S., Xu, R., Pellegrini, M., Riggs, A. D., and Fan, G. (2008). X-inactivation in female human embryonic stem cells is in a nonrandom pattern and prone to epigenetic alterations. Proc. Natl. Acad. Sci. U.S.A. 105, 4709-4714.
107. Silva, J., Mak, W., Zvetkova, I., Appanah, R., Nesterova, T. B., Webster, Z., Peters, A. H., Jenuwein, T., Otte, A. P., and Brockdorff, N. (2003). Establishment of histone h3 methylation on the inactive X chromosome requires transient recruitment of Eed-Enx1 polycomb group complexes. Dev. Cell 4, 481-495.
108. Silva, J., and Smith, A. (2008). Capturing pluripotency. Cell 132, 532-536.
109. Silva, S. S., Rowntree, R. K., Mekhoubad, S., and Lee, J. T. (2008). X-chromosome inactivation and epigenetic fluidity in human embryonic stem cells. Proc. Natl. Acad. Sci. U.S.A. 105, 4820-4825.
110. Skene, P. J., Illingworth, R. S., Webb, S., Kerr, A. R., James, K. D., Turner, D. J., Andrews, R., and Bird, A. P. (2010). Neuronal MeCP2 is expressed at near histoneoctamer levels and globally alters the chromatin state. Mol. Cell 37, 457-468.
111. Skuse, D. H. (2005). X-linked genes and mental functioning. Hum. Mol. Genet. 14, R27-R32.
112. Smith, A. G., Heath, J. K., Donaldson, D. D., Wong, G. G., Moreau, J., Stahl, M., and Rogers, D. (1988). Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides. Nature 336, 688-690.
113. Stadtfeld, M., Maherali, N., Breault, D. T., and Hochedlinger, K. (2008a). Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse. Cell Stem Cell 2, 230-240.
114. Stadtfeld, M., Nagaya, M., Utikal, J., Weir, G., and Hochedlinger, K. (2008b). Induced pluripotent stem cells generated without viral integration. Science 322, 945-949.
115. Stavridis, M. P., Lunn, J. S., Collins, B. J., and Storey, K. G. (2007). A discrete period of FGF-induced Erk1/2 signalling is required for vertebrate neural specification. Development 134, 2889-2894.
116. Takagi, N., Sugawara, O., and Sasaki, M. (1982). Regional and temporal changes in the pattern of X-chromosome replication during the early postimplantation development of the female mouse. Chromosoma 85, 275-286.
117. Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., and Yamanaka, S. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861-872.
118. Tan, J., Yang, X., Zhuang, L., Jiang, X., Chen, W., Lee, P. L., Karuturi, R. K., Tan, P. B., Liu, E. T., and Yu, Q. (2007). Pharmacologic disruption of polycombrepressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells. Genes Dev. 21, 1050-1063.
119. Tchieu, J., Kuoy, E., Chin, M. H., Trinh, H., Patterson, M., Sherman, S. P., Aimiuwu, O., Lindgren, A., Hakimian, S., Zack, J. A., Clark, A. T., Pyle, A. D., Lowry, W. E., and Plath, K. (2010). Female human iPSCs retain an inactive X chromosome. Cell Stem Cell 7, 329-342.
120. Tesar, P. J., Chenoweth, J. G., Brook, F. A., Davies, T. J., Evans, E. P., Mack, D. L., Gardner, R. L., and McKay, R. D. (2007). New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature 448, 196-199.
121. Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S., and Jones, J. M. (1998). Embryonic stem cell lines derived from human blastocysts. Science 282, 1145-1147.
122. Tian, D., Sun, S., and Lee, J. T. (2010). The long noncoding RNA, Jpx, is a molecular switch for X chromosome inactivation. Cell 143, 390-403.
123. Urbach, A., Bar-Nur, O., Daley, G. Q., and Benvenisty, N. (2010). Differential modeling of fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells. Cell Stem Cell 6, 407-411.
124. Vallier, L., Reynolds, D., and Pedersen, R. A. (2004). Nodal inhibits differentiation of human embryonic stem cells along the neuroectodermal default pathway. Dev. Biol. 275, 403-421.
125. van den Berg, I. M., Galjaard, R. J., Laven, J. S., and van Doorninck, J. H. (2011). XCI in preimplantation mouse and human embryos: first there is remodelling. Hum. Genet. 130, 203-215.
126. van den Berg, I. M., Laven, J. S., Stevens, M., Jonkers, I., Galjaard, R. J., Gribnau, J., and van Doorninck, J. H. (2009). X chromosome inactivation is initiated in human preimplantationembryos. Am. J. Hum. Genet.84, 771-779.
127. Walsh, R. M., and Hochedlinger, K. (2010). Modeling Rett syndrome with stem cells. Cell 143, 499-500.
128. Ware, C. B., Wang, L., Mecham, B. H., Shen, L., Nelson, A. M., Bar, M., Lamba, D. A., Dauphin, D. S., Buckingham, B., Askari, B., Lim, R., Tewari, M., Gartler, S. M., Issa, J. P., Pavlidis, P., Duan, Z., and Blau, C. A. (2009). Histone deacetylase inhibition elicits an evolutionarily conserved selfrenewal program in embryonic stem cells. Cell Stem Cell 4, 359-369.
129. Warren, L., Manos, P. D., Ahfeldt, T., Loh, Y. H., Li, H., Lau, F., Ebina, W., Mandal, P. K., Smith, Z. D., Meissner, A., Daley, G. Q., Brack, A. S., Collins, J. J., Cowan, C., Schlaeger, T. M., and Rossi, D. J. (2010). Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 7, 618-630.
130. Williams, R. L., Hilton, D. J., Pease, S., Willson, T. A., Stewart, C. L., Gearing, D. P., Wagner, E. F., Metcalf, D., Nicola, N. A., and Gough, N. M. (1988). Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells. Nature 336, 684-687.
131. Wutz, A., and Jaenisch, R. (2000). A shift from reversible to irreversible X inactivation is triggered during ES cell differentiation. Mol. Cell 5, 695-705.
132. Yang, C., Chapman, A. G., Kelsey, A. D., Minks, J., Cotton, A. M., and Brown, C. J. (2011). X-chromosome inactivation: molecular mechanisms from the human perspective. Hum. Genet. 130, 175-185.
133. Ying, Q. L., Nichols, J., Chambers, I., and Smith, A. (2003). BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell selfrenewal in collaboration with STAT3. Cell 115, 281-292.
134. Ying, Q. L., Wray, J., Nichols, J., Batlle-Morera, L., Doble, B., Woodgett, J., Cohen, P., and Smith, A. (2008). The ground state of embryonic stem cell selfrenewal. Nature 453, 519-523.
135. Yu, J., Hu, K., Smuga-Otto, K., Tian, S., Stewart, R., Slukvin, II, and Thomson, J. A. (2009). Human induced pluripotent stem cells free of vector and transgene sequences. Science 324, 797-801.
136. Yu, J., Vodyanik, M. A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J. L., Tian, S., Nie, J., Jonsdottir, G. A., Ruotti, V., Stewart, R., Slukvin, II, and Thomson, J. A. (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science 318, 1917-1920.
137. Zhang, L. F., Huynh, K. D., and Lee, J. T. (2007). Perinucleolar targeting of the inactive X during S phase: evidence for a role in the maintenance of silencing. Cell 129, 693-706.
138. Zhu, H., Lensch, M. W., Cahan, P., and Daley, G. Q. (2011). Investigating monogenic and complex diseases with pluripotent stem cells. Nat. Rev. Genet. 12, 266-275.
139. Zvetkova, I., Apedaile, A., Ramsahoye, B., Mermoud, J. E., Crompton, L. A., John, R., Feil, R., and Brockdorff, N. (2005). Global hypomethylation of the genome in XX embryonic stem cells. Nat. Genet. 37, 1274-1279.