Multiple layers of molecular controls modulate self-renewal and neuronal lineage specification of embryonic stem cells

Human Molecular Genetics

Volumn 17, Issue R1, 2008, Pages

  Yeo, Gene W ^a   Coufal, Nicole ^a   Aigner, Stefan ^a   Winner, Beate ^a   Scolnick, Jonathan A ^a   Marchetto, Maria C N ^a   Muotri, Alysson R ^a   Carson, Christian ^b   Gage, Fred H ^a  

^a SALK INSTITUTE FOR BIOLOGICAL STUDIES   (United States)

^b BD BIOSCIENCES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MICRORNA;

ALTERNATIVE RNA SPLICING; CELL FATE; CELL LINEAGE; CELL PROLIFERATION; CELL RENEWAL; CHROMATIN STRUCTURE; DEGENERATIVE DISEASE; EMBRYONIC STEM CELL; EPIGENETICS; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENETIC VARIABILITY; HUMAN; METHYLATION; NERVE CELL DIFFERENTIATION; NEURAL STEM CELL; NEUROLOGIC DISEASE; NONHUMAN; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; PROTEIN MODIFICATION; PROTEIN PROCESSING; REVIEW; STEM CELL TRANSPLANTATION; TRANSCRIPTOMICS;

ANIMALS; CELL DIFFERENTIATION; CELL PROLIFERATION; CHROMATIN; EMBRYONIC STEM CELLS; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION, DEVELOPMENTAL; HUMANS; MICRORNAS; MODELS, BIOLOGICAL; NEURODEGENERATIVE DISEASES; NEURONS; TISSUE THERAPY;

EID: 48049094961     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddn065     Document Type: Review

References (92)

1. Roy, N.S., Cleren, C., Singh, S.K., Yang, L., Beal, M.F. and Goldman, S.A. (2000) Functional engraftment of human ES cell-derived dopaminergic neurons enriched by coculture with telomerase-immortalized midbrain astrocytes. Nat. Med., 12, 1259-1268.
2. Nakagawa, M., Koyanagi, M., Tanabe, K., Takahashi, K., Ichisaka, T., Aoi, T., Okita, K., Mochiduki, Y., Takizawa, N. and Yamanaka, S. (2008) Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol, 26, 101-106.
3. 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.
4. Kawasaki, H., Mizuseki, K., Nishikawa, S., Kaneko, S., Kuwana, Y., Nakanishi, S., Nishikawa, S.I. and Sasai, Y. (2000) Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity. Neuron, 28, 31-40.
5. Perrier, A.L., Tabar, V., Barberi, T., Rubio, M.E., Bruses, J., Topf, N., Harrison, N.L. and Studer, L. (2004) Derivation of midbrain dopamine neurons from human embryonic stem cells. Proc. Natl. Acad. Sci. USA 101, 12543-12548.
6. Joannides, A.J., Fiore-Heriche, C., Battersby, A.A., Athauda-Arachchi, P., Bonbon, I.A., Williams, L., Westmore, K., Kemp, P.J., Compston, A., Allen, N.D. et al. (2007) A scaleable and defined system for generating neural stem cells from human embryonic stem cells. Stem Cells, 25, 731-737.
7. Itsykson, P., Ilouz, N., Turetsky, T., Goldstein, R.S., Pera, M.F., Eishbein, I., Segal, M. and Reubinoff, B.E. (2005) Derivation of neural precursors from human embryonic stem cells in the presence of noggin. Mol. Cell. Neurosci., 30, 24-36.
8. Zhang, S.C., Wernig, M., Duncan, I.D., Brustle, O. and Thomson, J.A. (2001) In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nat. Biotechnol., 19, 1129-1133.
9. Schulz, T.C., Palmarini, G.M., Noggle, S.A., Weiler, D.A., Mitalipova, M.M. and Condie, B.G. (2003) Directed neuronal differentiation of human embryonic stem cells. BMC Neurosci., 4, 27.
10. Sonntag, K.C., Pruszak, J., Yoshizaki, T., van Arensbergen, J., Sanchez-Pernaute, R. and Isacson, O. (2007) Enhanced yield of neuroepithelial precursors and midbrain-like dopaminergic neurons from human embryonic stem cells using the bone morphogenic protein antagonist noggin. Stem Cells, 25, 411-418.
11. Pera, M.F., Andrade, J., Houssami, S., Reubinoff, B., Trounson, A., Stanley, E.G., Ward-van Oostwaard, D. and Mummery, C. (2004) Regulation of human embryonic stem cell differentiation by BMP-2 and its antagonist noggin. J. Cell Sci., 117, 1269-1280.
12. Yeo, G.W., Xu, X., Liang, T.Y., Muotri, A.R., Carson, C.T., Coufal, N.G. and Gage, F.H. (2007) Alternative splicing events identified in human embryonic stem cells and neural progenitors. PLoS Comput. Biol., 3, e196.
13. Yan, Y., Yang, D., Zarnowska, E.D., Du, Z., Werbel, B., Valliere, C., Pearce, R.A., Thomson, J.A. and Zhang, S.C. (2005) Directed differentiation of dopaminergic neuronal subtypes from human embryonic stem cells. Stem Cells, 23, 781-790.
14. Schulz, T.C., Noggle, S.A., Palmarini, G.M., Weiler, D.A., Lyons, I.G., Pensa, K.A., Meedeniya, A.C., Davidson, B.P., Lambert, N.A. and Condie, B.G. (2004) Differentiation of human embryonic stem cells to dopaminergic neurons in serum-free suspension culture. Stem Cells, 22, 1218-1238.
15. Iacovitti, L., Donaldson, A.E., Marshall, C.E., Suon, S. and Yang, M. (2007) A protocol for the differentiation of human embryonic stem cells into dopaminergic neurons using only chemically defined human additives: studies in vitro and in vivo. Brain Res., 1127, 19-25.
16. Lee, H., Shamy, G.A., Elkabetz, Y., Schofield, C.M., Harrsion, N.L., Panagiotakos, G., Socci, N.D., Tabar, V. and Studer, L. (2007) Directed differentiation and transplantation of human embryonic stem cell-derived motoneurons. Stem Cells, 25, 1931-1939.
17. Li, X.J., Du, Z.W., Zarnowska, E.D., Pankratz, M., Hansen, L.O., Pearce, R.A. and Zhang, S.C. (2005) Specification of motoneurons from human embryonic stem cells. Nat. Biotechnol., 23, 215-221.
18. Yang, D., Zhang, Z.J., Oldenburg, M., Ayala, M. and Zhang, S.C. (2008) Human embryonic stem cell-derived doparminergic neurons reverse functional deficit in Parkinsonian rats. Stem Cells, 26, 55-63.
19. Brokhman, I., Gamarnik-Ziegler, L., Pomp, O., Aharonowiz, M., Reubinoff, B.E. and Goldstein, R.S. (2007) Peripheral sensory neurons differentiate from neural precursors derived from human embryonic stem cells. Differentiation, 76, 145-155.
20. Soundararajan, P., Miles, G.B., Rubin, L.L., Brownstone, R.M. and Rafuse, V.F. (2006) Motoneurons derived from embryonic stem cells express transcription factors and develop phenotypes characteristic of medial motor column neurons. J Neurosci, 26, 3256-3268.
21. Pruszak, J., Sonntag, K.C., Aung, M.H., Sanchez-Pernaute, R. and Isacson, O. (2007) Markers and methods for cell sorting of human embryonic stem cell-derived neural cell populations. Stem Cells, 25, 2257-2268.
22. Uchida, N., Buck, D.W., He, D., Reitsma, M.J., Masek, M., Phan, T.V., Tsukamoto, A.S., Gage, F.H. and Weissman, I.L. (2000) Direct isolation of human central nervous system stem cells. Proc. Natl. Acad. Sci. USA, 97, 14720-14725.
23. Barraud, P., Stott, S., Mollgard, K., Parmar, M. and Bjorklund, A. (2007) In vitro characterization of a human neural progenitor cell coexpressing SSEA4 and CD133. J. Neurosci. Res., 85, 250-259.
24. Piao, J.H., Odeberg, J., Samuelsson, E.B., Kjaeldgaard, A., Falci, S., Seiger, A., Sundstrom, E. and Akesson, E. (2006) Cellular composition of long-term human spinal cord- and forebrain-derived neurosphere cultures. J Neurosci Res, 84, 471-482.
25. Pan, G. and Thomson, J.A. (2007) Nanog and transcriptional networks in embryonic stem cell pluripotency. Cell Res., 17, 42-49.
26. Ringrose, L. and Paro, R. (2004) Epigenetic regulation of cellular memory by the Polycomb and Trithorax group proteins. Annu. Rev. Genet., 38, 413-443.
27. Boyer, L.A., Plath, K., Zeitlinger, J., Brambrink, T., Medeiros, L.A., Lee, T.I., Levine, S.S., Wernig, M., Tajonar, A., Ray, M.K. et al. (2006) Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature, 441, 349-353.
28. Voncken, J.W. (2003) Genetic modification of the mouse. General technology; pronuclear and blastocyst injection. Methods Mol. Biol. 209, 9-34.
29. O'Carroll, D., Erhardt, S., Pagani, M., Barton, S.C., Surani, M.A. and Jenuwein, T. (2001) The polycomb-group gene Ezh2 is required for early mouse development. Mol. Cell Biol., 21, 4330-4336.
30. Cao, R., Wang, L., Wang, H., Xia, L., Erdjument-Bromage, H., Tempst, P., Jones, R.S. and Zhang, Y. (2002) Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science, 298, 1039-1043.
31. Bernstein, E., Duncan, E.M., Masui, O., Gil, J., Heard, E. and Allis, C.D. (2006) Mouse polycomb proteins bind differentially to methylated historic H3 and RNA and are enriched in facultative heterochromatin. Mol. Cell Biol., 26, 2560-2569.
32. Azuara, V., Perry, P., Sauer, S., Spivakov, M., Jorgensen, H.F., John, R.M., Gouti, M., Casanova, M., Warnes, G., Merkenschlager, M. et al. (2006) Chromatin signatures of pluripotent cell lines. Nat. Cell Biol., 8, 532-538.
33. Boyer, L.A., Lee, T.I., Cole, M.F., Johnstone, S.E., Levine, S.S., Zucker, J.P., Guenther, M.G., Kumar, R.M., Murray, H.L., Jenner, R.G. et al. (2005) Core transcriptional regulatory circuitry in human embryonic stem cells. Cell, 122, 947-956.
34. Lee, T.I., Jenner, R.G., Boyer, L.A., Guenther, M.G., Levine, S.S., Kumar, R.M., Chevalier, B., Johnstone, S.E., Cole, M.F., Isono, K. et al. (2006) Control of developmental regulators by Polycomb in human embryonic stem cells. Cell, 125, 301-313.
35. Mikkelsen, T.S., Ku, M., Jaffe, D.B., Issac, B., Lieberman, E., Giannoukos, G., Alvarez, P., Brockman, W., Kim, T.K., Koche, R.P. et al. (2007) Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature, 448, 553-560.
36. Xu, J., Pope, S.D., Jazirehi, A.R., Attema, J.L., Papathanasiou, P., Watts, J.A., Zaret, K.S., Weissman, I.L. and Smale, S.T. (2007) Pioneer factor interactions and unmethylated CpG dinucleotides mark silent tissue-specific enhancers in embryonic stem cells. Proc. Natl. Acad. Sci. USA, 104, 12377-12382.
37. Calabrese, I.M., Seila, A.C., Yeo, G.W. and Sharp, P.A. (2007) RNA sequence analysis defines Dicer's role in mouse embryonic stem cells. Proc. Natl. Acad. Sci. USA, 104, 18097-18102.
38. Du, T. and Zamore, P.D. (2007) Beginning to understand microRNA function. Cell Res., 17, 661-663.
39. Standart, N. and Jackson, R.J. (2007) MicroRNAs repress translation of m7Gppp-capped target mRNAs in vitro by inhibiting initiation and promoting deadenylation. Genes Dev., 21, 1975-1982.
40. Karginov, F.V., Conaco, C., Xuan, Z., Schmidt, B.H., Parker, J.S., Mandel, G. and Hannon, G.J. (2007) A biochemical approach to identifying microRNA targets. Proc. Natl. Acad. Sci. USA, 104, 19291-19296.
41. Lim, L.P., Lau, N.C., Garrett-Engele, P., Grimson, A., Schelter, J.M., Castle, J., Bartel, D.P., Linsley, P.S. and Johnson, J.M. (2005) Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature, 433, 769-773.
42. Kim, J., Inoue, K., Ishii, J., Vanti, W.B., Voronov, S.V., Murchison, E., Hannon, G. and Abeliovich, A. (2007) A microRNA feedback circuit in midbrain dopamine neurons. Science, 317, 1220-1224.
43. Krutzfeldt, J., Rajewsky, N., Braich, R., Rajoev, K.G., Tuschl, T., Manoharan, M. and Stoffel, M. (2005) Silencing of microRNAs in vivo with 'antagomirs'. Nature, 438, 685-689.
44. Vermeulen, A., Robertson, B., Dalby, A.B., Marshall, W.S., Karpilow, J., Leake, D., Khvorova, A. and Baskerville, S. (2007) Double-stranded regions are essential design components of potent inhibitors of RISC function. RNA, 13, 723-730.
45. Berg, D., Niwar, M., Maass, S., Zimprich, A., Moller, J.C., Wuellner, U., Schmitz-Hubsch, T., Klein, C., Tan, E.K., Schols, L. et al. (2005) Alpha-synuclein and Parkinson's disease: Implications from the screening of more than 1,900 patients. Mov. Disord.
46. Cao, X., Pfaff, S.L. and Gage, F.H. (2007) A functional study of miR-124 in the developing neural tube. Genes Dev., 21, 531-536.
47. Schratt, G.M., Tuebing, F., Nigh, E.A., Kane, C.G., Sabatini, M.E., Kiebler, M. and Greenberg, M.E. (2006) A brain-specific microRNA regulates dendritic spine development Nature, 439, 283-289.
48. Kanellopoulou, C., Muljo, S.A., Kung, A.L., Ganesan, S., Drapkin, R., Jenuwein, T., Livingston, D.M. and Rajewsky, K. (2005) Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev., 19, 489-501.
49. Murchison, E.P., Partridge, J.F., Tam, O.H., Cheloufi, S. and Hannon, G.J. (2005) Characterization of Dicer-deficient murine embryonic stem cells. Proc. Natl. Acad. Sci. USA, 102, 12135-12140.
50. Wang, Y., Medvid, R., Melton, C., Jaenisch, R. and Blelloch, R. (2007) DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal. Nat. Genet., 39, 380-385.
51. Liu, N., Lu, M., Tian, X. and Han, Z. (2007) Molecular mechanisms involved in self-renewal and pluripotency of embryonic stem cells. J. Cell Physiol., 211, 279-286.
52. Houbaviy, H.B., Murray, M.F. and Sharp, P.A. (2003) Embryonic stem cell-specific MicroRNAs. Dev. Cell, 5, 351-358.
53. Suh, M.R., Lee, Y., Kim, J.Y., Kim, S.K., Moon, S.H., Lee, J.Y., Cha, K.Y., Chung, H.M., Yoon, H.S., Moon, S.Y. et al. (2004) Human embryonic stem cells express a unique set of microRNAs. Dev. Biol. 270, 488-498.
54. Voorhoeve, P.M., le Sage, C., Schrier, M., Gillis, A.J., Stoop, H., Nagel, R., Liu, Y.P., van Duijse, J., Drost, J., Griekspoor, A. et al. (2006) A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell, 124, 1169-1181.
55. Hatfield, S.D., Shcherbata, H.R., Fischer, K.A., Nakahara, K., Carthew, R.W. and Ruohola-Baker, H. (2005) Stem cell division is regulated by the microRNA pathway. Nature, 435, 974-978.
56. Tay, Y.M., Tam, W.L., Ang, Y.S., Gaughwin, P.M., Yang, H.H., Wang, W., Liu, R., George, J., Ng, H.H., Perera, R.J. et al. (2008) MicroRNA-134 modulates the differentiation of mouse embryonic stem cells where it causes post-transcriptional attenuation of Nanog and LRH1. Stem Cells, 26, 17-29.
57. Krichevsky, A.M., Sonntag, K.C., Isacson, O. and Kosik, K.S. (2006) Specific microRNAs modulate embryonic stem cell-derived neurogenesis. Stem Cells, 24, 857-864.
58. Abeyta, M.J., Clark, A.T., Rodriguez, R.T., Bodnar, M.S., Pera, R.A. and Firpo, M.T. (2004) Unique gene expression signatures of independently-derived human embryonic stem cell lines. Hum. Mol. Genet., 13, 601-608.
59. Wu, H., Xu, J., Pang, Z.P., Ge, W., Kim, K.J., Blanchi, B., Chen, C., Sudhof, T.C. and Sun, Y.E. (2007) Integrative genomic and functional analyses reveal neuronal subtype differentiation bias in human embyronic stem cell lines. Proc. Natl. Acad. Sci. USA, 104, 13821-13826.
60. Cai, J., Chen, J., Liu, Y., Miura, T., Luo, Y., Loring, J.F., Freed, W.J., Rao, M.S. and Zeng, X. (2006) Assessing self-renewal and differentiation in human embryonic stem cell lines. Stem Cells, 24, 516-530.
61. Bhattacharya, B., Cai, J., Luo, Y., Miura, T., Mejido, J., Brimble, S.N., Zeng, X., Schulz, T.C., Rao, M.S. and Puri, R.K. (2005) Comparison of the gene expression profile of undifferentiated human embryonic stem cell lines and differentiating embryoid bodies. BMC Dev. Biol., 5, 22.
62. Miura, T., Luo, Y., Khrebtukova, I., Brandenberger, R., Zhou, D., Thies, R.S., Vasicek, T., Young, H., Lebkowski, J., Carpenter, M.K. et al. (2004) Monitoring early differentiation events in human embryonic stem cells by massively parallel signature sequencing and expressed sequence tag scan. Stem Cells Dev., 13, 694-715.
63. Brandenberger, R., Wei, H., Zhang, S., Lei, S., Murage, J., Fisk, G.J., Li, Y., Xu, C., Fang, R., Guegler, K. et al. (2004) Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. Nat. Biotechnol., 22, 707-716.
64. Brandenberger, R., Khrebtukova, I., Thies, R.S., Miura, T., Jingli, C., Puri, R., Vasicek, T., Lebkowski, J. and Rao, M. (2004) MPSS profiling of human embryonic stem cells. BMC Dev. Biol., 4, 10.
65. Wright, L.S., Li, J., Caldwell, M.A., Wallace, K., Johnson, J.A. and Svendsen, C.N. (2003) Gene expression in human neural stem cells: effects of leukemia inhibitory factor. J. Neurochem., 86, 179-195.
66. Cai, J., Shin, S., Wright, L., Liu, Y., Zhou, D., Xue, H., Khrebtukova, I., Mattson, M.P., Svendsen, C.N. and Rao, M.S. (2006) Massively parallel signature sequencing profiling of fetal human neural precursor cells. Stem Cells Dev., 15, 232-244.
67. Maisel, M., Herr, A., Milosevic, J., Hermann, A., Habisch, H.J., Schwarz, S., Kirsch, M., Antoniadis, G., Brenner, R., Hallmeyer-Elgner, S. et al. (2007) Transcription profiling of adult and fetal human neuroprogenitors identifies divergent paths to maintain the neuroprogenitor cell state. Stem Cells.
68. Richards, M., Tan, S.P., Tan, J.H., Chan, W.K. and Bongso, A. (2004) The transcriptome profile of human embryonic stem cells as defined by SAGE. Stem Cells, 22, 51-64.
69. Black, D.L. (2003) Mechanisms of alternative pre-messenger RNA splicing. Annu. Rev. Biochem., 72, 291-336.
70. Cartegni, L., Chew, S.L. and Krainer, A.R. (2002) Listening to silence and understanding nonsense: Exonic mutations that affect splicing. Nat. Rev. Genet., 3, 285-298.
71. Graveley, B.R. (2001) Alternative splicing: Increasing diversity in the proteomic world. Trends Genet., 17, 100-107.
72. Zavolan, M., Kondo, S., Schonbach, C., Adachi, J., Hume, D.A., Hayashizaki, Y. and Gaasterland, T. (2003) Impact of alternative initiation, splicing, and termination on the diversity of the mRNA transcripts encoded by the mouse transcriptome. Genome Res., 13 1290-1300.
73. Blencowe, B.J. (2006) Alternative splicing: New insights from global analyses. Cell, 126, 37-47.
74. Black, D.L. and Grabowski, P.J. (2003) Alternative pre-mRNA splicing and neuronal function. Prog. Mol. Subcell. Biol., 31, 187-216.
75. Grabowski, P.J. and Black, D.L. (2001) Alternative RNA splicing in the nervous system. Prog. Neurobiol., 65, 289-308.
76. Matlin, A.J., Clark, F. and Smith, C.W. (2005) Understanding alternative splicing: Towards a cellular code. Nat. Rev. Mol. Cell Biol., 6 386-398.
77. Wang, G.S. and Cooper, T.A. (2007) Splicing in disease: Disruption of the splicing code and the decoding machinery. Nat. Rev. Genet., 8, 749-761.
78. Spellman, R., Llorian, M. and Smith, C.W. (2007) Crossregulation and functional redundancy between the splicing regulator PTB and its paralogs nPTB and ROD1. Mol. Cell, 27, 420-434.
79. Makeyev, E.V., Zhang, J., Carrasco, M.A. and Maniatis, T. (2007) The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol. Cell, 27, 435-448.
80. Boutz, P.L., Stoilov, P., Li, Q., Lin, C.H., Chawla, G., Ostrow, K., Shiue, L., Ares, M., Jr and Black, D.L. (2007) A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons. Genes Dev., 21, 1636-1652.
81. Ashiya, M. and Grabowski, P.J. (1997) A neuron-specific splicing switch mediated by an array of pre-mRNA repressor sites: Evidence of a regulatory role for the polypyrimidine tract binding protein and a brain-specific PTB counterpart. RNA, 3, 996-1015.
82. Mayshar, Y., Rom, E., Chumakov, I., Kronman, A., Yayon, A. and Benvenisty, N. (2008) FGF4 and its novel splice isoform have opposing effects on the maintenance of human embryonic stem cell self renewal. Stem Cells.
83. Pritsker, M., Doniger, T.T., Kramer, L.C., Westcot, S.E. and Lemischka, I.R. (2005) Diversification of stem cell molecular repertoire by alternative splicing. Proc. Natl. Acad. Sci. USA, 102, 14290-14295.
84. Zhang, Z., Liao, B., Xu, M. and Jin, Y. (2007) Post-translational modification of POU domain transcription factor Oct-4 by SUMO-1. FASEB J., 21, 3042-3051.
85. Puente, L.G., Borris, D.J., Carriere, J.F., Kelly, J.F. and Megeney, L.A. (2006) Identification of candidate regulators of embryonic stem cell differentiation by comparative phosphoprotein affinity profiling. Mol. Cell Proteomics, 5, 57-67.
86. Brown, R. and Strathdee, G. (2002) Epigenomics and epigenetic therapy of cancer. Trends Mol. Med., 8, S43-S48.
87. Hsieh, J., Nakashima, K., Kuwabara, T., Mejia, E. and Gage, F.H. (2004) Histone deacetylase inhibition-mediated neuronal differentiation of multipotent adult neural progenitor cells. Proc. Natl. Acad. Sci. USA 101, 16659-16664.
88. Lyssiotis, C.A., Walker, J., Wu, C., Kondo, T., Schultz, P.G. and Wu, X. (2007) Inhibition of histone deacetylase activity induces developmental plasticity in oligodendrocyte precursor cells. Proc. Natl. Acad. Sci. USA, 104, 14982-14987.
89. Lykke-Andersen, K. (2006) Regulation of gene expression in mouse embryos and its embryonic cells through RNAi. Mol. Biotechnol., 34, 271-278.
90. Ding, L. and Buchholz, F. (2006) RNAi in embryonic stem cells. Stem Cell Rev., 2, 11-18.
91. Wang, J., Theunissen, T.W. and Orkin, S.H. (2007) Site-directed, virus-free, and inducible RNAi in embryonic stem cells. Proc. Natl. Acad. Sci. USA, 104, 20850-20855.
92. Spivakov, M. and Fisher, A.G. (2007) Epigenetic signatures of stem-cell identity. Nat. Rev. Genet., 8, 263-271.