Table of Contents Author Guidelines Submit a Manuscript
Comparative and Functional Genomics
Volume 2012 (2012), Article ID 564381, 10 pages
http://dx.doi.org/10.1155/2012/564381
Review Article

Epigenetic Regulation of B Lymphocyte Differentiation, Transdifferentiation, and Reprogramming

1Cellular Differentiation Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Avenida Gran Via s/n km 2.7, 08907 L’Hospitalet de Llobregat, Barcelona, Spain
2Department of Biochemistry, Erasmus University Medical Center, Ee622, P.O.Box 2040, 3000 CA Rotterdam, The Netherlands

Received 7 February 2012; Revised 21 May 2012; Accepted 6 July 2012

Academic Editor: Sonia Vanina Forcales

Copyright © 2012 Bruna Barneda-Zahonero et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. Adolfsson, R. Månsson, N. Buza-Vidas et al., “Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential: a revised road map for adult blood lineage commitment,” Cell, vol. 121, no. 2, pp. 295–306, 2005. View at Publisher · View at Google Scholar · View at Scopus
  2. T. Yoshida, S. Yao-Ming Ng, J. C. Zuniga-Pflucker, and K. Georgopoulos, “Early hematopoietic lineage restrictions directed by Ikaros,” Nature Immunology, vol. 7, no. 4, pp. 382–391, 2006. View at Publisher · View at Google Scholar · View at Scopus
  3. H. Igarashi, S. C. Gregory, T. Yokota, N. Sakaguchi, and P. W. Kincade, “Transcription from the RAG1 locus marks the earliest lymphocyte progenitors in bone marrow,” Immunity, vol. 17, no. 2, pp. 117–130, 2002. View at Publisher · View at Google Scholar · View at Scopus
  4. M. Kondo, I. L. Weissman, and K. Akashi, “Identification of clonogenic common lymphoid progenitors in mouse bone marrow,” Cell, vol. 91, no. 5, pp. 661–672, 1997. View at Google Scholar · View at Scopus
  5. C. Cobaleda and M. Busslinger, “Developmental plasticity of lymphocytes,” Current Opinion in Immunology, vol. 20, no. 2, pp. 139–148, 2008. View at Publisher · View at Google Scholar · View at Scopus
  6. G. Natoli, “Maintaining cell identity through global control of genomic organization,” Immunity, vol. 33, no. 1, pp. 12–24, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. G. Bain, E. C. R. Maandag, D. J. Izon et al., “E2A proteins are required for proper b cell development and initiation of immunoglobulin gene rearrangements,” Cell, vol. 79, no. 5, pp. 885–892, 1994. View at Publisher · View at Google Scholar · View at Scopus
  8. G. Bain, E. C. Robanus Maandag, H. P. J. Te Riele et al., “Both E12 and E47 allow commitment to the B cell lineage,” Immunity, vol. 6, no. 2, pp. 145–154, 1997. View at Publisher · View at Google Scholar · View at Scopus
  9. Y. Zhuang, P. Soriano, and H. Weintraub, “The helix-loop-helix gene E2A is required for B cell formation,” Cell, vol. 79, no. 5, pp. 875–884, 1994. View at Publisher · View at Google Scholar · View at Scopus
  10. H. Lin and R. Grosschedl, “Failure of B-cell differentiation in mice lacking the transcription factor EBF,” Nature, vol. 376, no. 6537, pp. 263–267, 1995. View at Publisher · View at Google Scholar · View at Scopus
  11. H. S. Dengler, G. V. Baracho, S. A. Omori et al., “Distinct functions for the transcription factor Foxo1 at various stages of B cell differentiation,” Nature Immunology, vol. 9, no. 12, pp. 1388–1398, 2008. View at Publisher · View at Google Scholar · View at Scopus
  12. P. Urbanek, Z. Q. Wang, I. Fetka, E. F. Wagner, and M. Busslinger, “Complete block of early B cell differentiation and altered patterning of the posterior midbrain in mice lacking Pax5/BSAP,” Cell, vol. 79, no. 5, pp. 901–912, 1994. View at Publisher · View at Google Scholar · View at Scopus
  13. D. Allman, A. Jain, A. Dent et al., “BCL-6 expression during B-cell activation,” Blood, vol. 87, no. 12, pp. 5257–5268, 1996. View at Google Scholar · View at Scopus
  14. A. L. Dent, A. L. Shaffer, X. Yu, D. Allman, and L. M. Staudt, “Control of inflammation, cytokine expression, and germinal center formation by BCL-6,” Science, vol. 276, no. 5312, pp. 589–592, 1997. View at Publisher · View at Google Scholar · View at Scopus
  15. B. H. Ye, G. Cattoretti, Q. Shen et al., “The BCL-6 proto-oncogene controls germinal-centre formation and Th2- type inflammation,” Nature Genetics, vol. 16, no. 2, pp. 161–170, 1997. View at Publisher · View at Google Scholar · View at Scopus
  16. A. L. Shaffer, K. I. Lin, T. C. Kuo et al., “Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program,” Immunity, vol. 17, no. 1, pp. 51–62, 2002. View at Publisher · View at Google Scholar · View at Scopus
  17. R. Sciammas and M. M. Davis, “Modular nature of blimp-1 in the regulation of gene expression during B cell maturation,” Journal of Immunology, vol. 172, no. 9, pp. 5427–5440, 2004. View at Google Scholar · View at Scopus
  18. Y. C. Lin, S. Jhunjhunwala, C. Benner et al., “A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fate,” Nature Immunology, vol. 11, no. 7, pp. 635–643, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. S. McManus, A. Ebert, G. Salvagiotto et al., “The transcription factor Pax5 regulates its target genes by recruiting chromatin-modifying proteins in committed B cells,” EMBO Journal, vol. 30, no. 12, pp. 2388–2404, 2011. View at Publisher · View at Google Scholar · View at Scopus
  20. N. Novershtern, A. Subramanian, L. N. Lawton et al., “Densely interconnected transcriptional circuits control cell states in human hematopoiesis,” Cell, vol. 144, no. 2, pp. 296–309, 2011. View at Publisher · View at Google Scholar · View at Scopus
  21. H. Gao, K. Lukin, J. Ramírez, S. Fields, D. Lopez, and J. Hagman, “Opposing effects of SWI/SNF and Mi-2/NuRD chromatin remodeling complexes on epigenetic reprogramming by EBF and Pax5,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 27, pp. 11258–11263, 2009. View at Publisher · View at Google Scholar · View at Scopus
  22. K. Walter, C. Bonifer, and H. Tagoh, “Stem cell-specific epigenetic priming and B cell-specific transcriptional activation at the mouse Cd19 locus,” Blood, vol. 112, no. 5, pp. 1673–1682, 2008. View at Publisher · View at Google Scholar · View at Scopus
  23. I. H. Su and A. Tarakhovsky, “Epigenetic control of B cell differentiation,” Seminars in Immunology, vol. 17, no. 2, pp. 167–172, 2005. View at Publisher · View at Google Scholar · View at Scopus
  24. H. Kulessa, J. Frampton, and T. Graf, “GATA-1 reprograms avian myelomonocytic cell lines into eosinophils, thromboblasts, and erythroblasts,” Genes and Development, vol. 9, no. 10, pp. 1250–1262, 1995. View at Google Scholar · View at Scopus
  25. L. H. Bussmann, A. Schubert, T. P. Vu Manh et al., “A robust and highly efficient immune cell reprogramming system,” Cell Stem Cell, vol. 5, no. 5, pp. 554–566, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. S. L. Nutt, B. Heavey, A. G. Rolink, and M. Busslinger, “Commitment to the B-lymphoid lineage depends on the transcription factor Pax5,” Nature, vol. 401, no. 6753, pp. 556–562, 1999. View at Publisher · View at Google Scholar · View at Scopus
  27. J. Hanna, S. Markoulaki, P. Schorderet et al., “Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency,” Cell, vol. 133, no. 2, pp. 250–264, 2008. View at Publisher · View at Google Scholar · View at Scopus
  28. C. R. Clapier and B. R. Cairns, “The biology of chromatin remodeling complexes,” Annual Review of Biochemistry, vol. 78, pp. 273–304, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. S. Guil and M. Esteller, “DNA methylomes, histone codes and miRNAs: tying it all together,” International Journal of Biochemistry and Cell Biology, vol. 41, no. 1, pp. 87–95, 2009. View at Publisher · View at Google Scholar · View at Scopus
  30. T. Kouzarides, “Chromatin modifications and their function,” Cell, vol. 128, no. 4, pp. 693–705, 2007. View at Publisher · View at Google Scholar · View at Scopus
  31. J. K. Wiencke, S. Zheng, Z. Morrison, and R. F. Yeh, “Differentially expressed genes are marked by histone 3 lysine 9 trimethylation in human cancer cells,” Oncogene, vol. 27, no. 17, pp. 2412–2421, 2008. View at Publisher · View at Google Scholar · View at Scopus
  32. C. R. Vakoc, S. A. Mandat, B. A. Olenchock, and G. A. Blobel, “Histone H3 lysine 9 methylation and HP1γ are associated with transcription elongation through mammalian chromatin,” Molecular Cell, vol. 19, no. 3, pp. 381–391, 2005. View at Publisher · View at Google Scholar · View at Scopus
  33. K. Georgopoulos, M. Bigby, J. H. Wang et al., “The Ikaros gene is required for the development of all lymphoid lineages,” Cell, vol. 79, no. 1, pp. 143–156, 1994. View at Publisher · View at Google Scholar · View at Scopus
  34. J. H. Wang, A. Nichogiannopoulou, L. Wu et al., “Selective defects in the development of the fetal and adult lymphoid system in mice with an Ikaros null mutation,” Immunity, vol. 5, no. 6, pp. 537–549, 1996. View at Publisher · View at Google Scholar · View at Scopus
  35. S. Y. M. Ng, T. Yoshida, and K. Georgopoulos, “Ikaros and chromatin regulation in early hematopoiesis,” Current Opinion in Immunology, vol. 19, no. 2, pp. 116–122, 2007. View at Publisher · View at Google Scholar · View at Scopus
  36. J. Kim, S. Sif, B. Jones et al., “Ikaros DNA-binding proteins direct formation of chromatin remodeling complexes in lymphocytes,” Immunity, vol. 10, no. 3, pp. 345–355, 1999. View at Google Scholar · View at Scopus
  37. J. Zhang, A. F. Jackson, T. Naito et al., “Harnessing of the nucleosome-remodeling-deacetylase complex controls lymphocyte development and prevents leukemogenesis,” Nature Immunology, vol. 13, no. 1, pp. 86–94, 2012. View at Publisher · View at Google Scholar · View at Scopus
  38. S. R. McKercher, B. E. Torbett, K. L. Anderson et al., “Targeted disruption of the PU.1 gene results in multiple hematopoietic abnormalities,” EMBO Journal, vol. 15, no. 20, pp. 5647–5658, 1996. View at Google Scholar · View at Scopus
  39. E. W. Scott, M. C. Simon, J. Anastasi, and H. Singh, “Requirement of transcription factor PU.1 in the development of multiple hematopoietic lineages,” Science, vol. 265, no. 5178, pp. 1573–1577, 1994. View at Google Scholar · View at Scopus
  40. S. Heinz, C. Benner, N. Spann et al., “Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities,” Molecular Cell, vol. 38, no. 4, pp. 576–589, 2010. View at Publisher · View at Google Scholar · View at Scopus
  41. M. Ye and T. Graf, “Early decisions in lymphoid development,” Current Opinion in Immunology, vol. 19, no. 2, pp. 123–128, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. M. Busslinger, “Transcriptional control of early B cell development,” Annual Review of Immunology, vol. 22, pp. 55–79, 2004. View at Publisher · View at Google Scholar · View at Scopus
  43. A. S. Lazorchak, J. Wojciechowski, M. Dai, and Y. Zhuang, “E2A promotes the survival of precursor and mature B lymphocytes,” Journal of Immunology, vol. 177, no. 4, pp. 2495–2504, 2006. View at Google Scholar · View at Scopus
  44. R. H. Amin and M. S. Schlissel, “Foxo1 directly regulates the transcription of recombination-activating genes during B cell development,” Nature Immunology, vol. 9, no. 6, pp. 613–622, 2008. View at Publisher · View at Google Scholar · View at Scopus
  45. H. Maier, R. Ostraat, H. Gao et al., “Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcription,” Nature Immunology, vol. 5, no. 10, pp. 1069–1077, 2004. View at Publisher · View at Google Scholar · View at Scopus
  46. E. Mercer, Y. Lin, C. Benner et al., “Multilineage priming of enhancer repertoires precedes commitment to the B and myeloid cell lineages in hematopoietic progenitors,” Immunity, vol. 35, no. 3, pp. 413–425, 2011. View at Publisher · View at Google Scholar · View at Scopus
  47. T. Treiber, E. M. Mandel, S. Pott et al., “Early B cell factor 1 regulates B cell gene networks by activation, repression, and transcription- independent poising of chromatin,” Immunity, vol. 32, no. 5, pp. 714–725, 2010. View at Publisher · View at Google Scholar · View at Scopus
  48. X.-X. Jiang, Q. Nguyen, Y. Chou et al., “Control of B cell development by the histone H2A deubiquitinase MYSM1,” Immunity, vol. 35, no. 6, pp. 883–896, 2011. View at Publisher · View at Google Scholar · View at Scopus
  49. D. O'Carroll, I. Mecklenbrauker, P. P. Das et al., “A Slicer-independent role for Argonaute 2 in hematopoiesis and the microRNA pathway,” Genes and Development, vol. 21, no. 16, pp. 1999–2004, 2007. View at Publisher · View at Google Scholar · View at Scopus
  50. S. B. Koralov, S. A. Muljo, G. R. Galler et al., “Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage,” Cell, vol. 132, no. 5, pp. 860–874, 2008. View at Publisher · View at Google Scholar · View at Scopus
  51. C. Z. Chen, L. Li, H. F. Lodish, and D. P. Bartel, “MicroRNAs modulate hematopoietic lineage differentiation,” Science, vol. 303, no. 5654, pp. 83–86, 2004. View at Publisher · View at Google Scholar · View at Scopus
  52. B. Zhou, S. Wang, C. Mayr, D. P. Bartel, and H. F. Lodish, “miR-150, a microRNA expressed in mature B and T cells, blocks early B cell development when expressed prematurely,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 17, pp. 7080–7085, 2007. View at Publisher · View at Google Scholar · View at Scopus
  53. C. Xiao, D. P. Calado, G. Galler et al., “MiR-150 controls B cell differentiation by targeting the transcription factor c-Myb,” Cell, vol. 131, no. 1, pp. 146–159, 2007. View at Publisher · View at Google Scholar · View at Scopus
  54. A. Ventura, A. G. Young, M. M. Winslow et al., “Targeted deletion reveals essential and overlapping functions of the miR-17~92 family of miRNA clusters,” Cell, vol. 132, no. 5, pp. 875–886, 2008. View at Publisher · View at Google Scholar · View at Scopus
  55. R. M. O'Connell, D. S. Rao, A. A. Chaudhuri, and D. Baltimore, “Physiological and pathological roles for microRNAs in the immune system,” Nature Reviews Immunology, vol. 10, no. 2, pp. 111–122, 2010. View at Publisher · View at Google Scholar · View at Scopus
  56. S. Kuchen, W. Resch, A. Yamane et al., “Regulation of MicroRNA expression and abundance during lymphopoiesis,” Immunity, vol. 32, no. 6, pp. 828–839, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. C. Cobaleda, A. Schebesta, A. Delogu, and M. Busslinger, “Pax5: the guardian of B cell identity and function,” Nature Immunology, vol. 8, no. 5, pp. 463–470, 2007. View at Publisher · View at Google Scholar · View at Scopus
  58. T. Decker, M. Pasca di Magliano, S. McManus et al., “Stepwise activation of enhancer and promoter regions of the B cell commitment gene Pax5 in early lymphopoiesis,” Immunity, vol. 30, no. 4, pp. 508–520, 2009. View at Publisher · View at Google Scholar · View at Scopus
  59. A. Delogu, A. Schebesta, Q. Sun, K. Aschenbrenner, T. Perlot, and M. Busslinger, “Gene repression by Pax5 in B cells is essential for blood cell homeostasis and is reversed in plasma cells,” Immunity, vol. 24, no. 3, pp. 269–281, 2006. View at Publisher · View at Google Scholar · View at Scopus
  60. A. Schebesta, S. McManus, G. Salvagiotto, A. Delogu, G. A. Busslinger, and M. Busslinger, “Transcription factor Pax5 activates the chromatin of key genes involved in B cell signaling, adhesion, migration, and immune function,” Immunity, vol. 27, no. 1, pp. 49–63, 2007. View at Publisher · View at Google Scholar · View at Scopus
  61. C. Pridans, M. L. Holmes, M. Polli et al., “Identification of Pax5 target genes in early B cell differentiation,” Journal of Immunology, vol. 180, no. 3, pp. 1719–1728, 2008. View at Google Scholar · View at Scopus
  62. H. Tagoh, A. Schebesta, P. Lefevre et al., “Epigenetic silencing of the c-fms locus during B-lymphopoiesis occurs in discrete steps and is reversible,” EMBO Journal, vol. 23, no. 21, pp. 4275–4285, 2004. View at Publisher · View at Google Scholar · View at Scopus
  63. H. Tagoh, R. Ingram, N. Wilson et al., “The mechanism of repression of the myeloid-specific c-fms gene by Pax5 during B lineage restriction,” EMBO Journal, vol. 25, no. 5, pp. 1070–1080, 2006. View at Publisher · View at Google Scholar · View at Scopus
  64. V. Giambra, S. Volpi, A. V. Emelyanov et al., “Pax5 and linker histone H1 coordinate DNA methylation and histone modifications in the 3′ regulatory region of the immunoglobulin heavy chain locus,” Molecular and Cellular Biology, vol. 28, no. 19, pp. 6123–6133, 2008. View at Publisher · View at Google Scholar · View at Scopus
  65. K. Rajewsky, “Clonal selection and learning in the antibody system,” Nature, vol. 381, no. 6585, pp. 751–758, 1996. View at Publisher · View at Google Scholar · View at Scopus
  66. M. Kraus, M. B. Alimzhanov, N. Rajewsky, and K. Rajewsky, “Survival of resting mature B lymphocytes depends on BCR signaling via the Igα/β heterodimer,” Cell, vol. 117, no. 6, pp. 787–800, 2004. View at Publisher · View at Google Scholar · View at Scopus
  67. K. L. Calame, K. I. Lin, and C. Tunyaplin, “Regulatory mechanisms that determine the development and function of plasma cells,” Annual Review of Immunology, vol. 21, pp. 205–230, 2003. View at Publisher · View at Google Scholar · View at Scopus
  68. T. Honjo, M. Muramatsu, and S. Fagarasan, “Aid: how does it aid antibody diversity?” Immunity, vol. 20, no. 6, pp. 659–668, 2004. View at Publisher · View at Google Scholar · View at Scopus
  69. R. Reljic, S. D. Wagner, L. J. Peakman, and D. T. Fearon, “Suppression of signal transducer and activator of transcription 3-dependent B lymphocyte terminal differentiation by BCL-6,” Journal of Experimental Medicine, vol. 192, no. 12, pp. 1841–1847, 2000. View at Publisher · View at Google Scholar · View at Scopus
  70. A. L. Shaffer, X. Yu, Y. He, J. Boldrick, E. P. Chan, and L. M. Staudt, “BCL-6 represses genes that function in lymphocyte differentiation, inflammation, and cell cycle control,” Immunity, vol. 13, no. 2, pp. 199–212, 2000. View at Google Scholar · View at Scopus
  71. N. Fujita, D. L. Jaye, M. Kajita, C. Geigerman, C. S. Moreno, and P. A. Wade, “MTA3, a Mi-2/NuRD complex subunit, regulates an invasive growth pathway in breast cancer,” Cell, vol. 113, no. 2, pp. 207–219, 2003. View at Publisher · View at Google Scholar · View at Scopus
  72. N. Fujita, D. L. Jaye, C. Geigerman et al., “MTA3 and the Mi-2/NuRD complex regulate cell fate during B lymphocyte differentiation,” Cell, vol. 119, no. 1, pp. 75–86, 2004. View at Publisher · View at Google Scholar · View at Scopus
  73. I. Gyory, J. Wu, G. Fejér, E. Seto, and K. L. Wright, “PRDI-BF1 recruits the histone H3 methyltransferase G9a in transcriptional silencing,” Nature Immunology, vol. 5, no. 3, pp. 299–308, 2004. View at Publisher · View at Google Scholar · View at Scopus
  74. K. Ancelin, U. C. Lange, P. Hajkova et al., “Blimp1 associates with Prmt5 and directs histone arginine methylation in mouse germ cells,” Nature Cell Biology, vol. 8, no. 6, pp. 623–630, 2006. View at Publisher · View at Google Scholar · View at Scopus
  75. S. T. Su, H. Y. Ying, Y. K. Chiu, F. R. Lin, M. Y. Chen, and K. I. Lin, “Involvement of histone demethylase LSD1 in blimp-1-mediated gene repression during plasma cell differentiation,” Molecular and Cellular Biology, vol. 29, no. 6, pp. 1421–1431, 2009. View at Publisher · View at Google Scholar · View at Scopus
  76. A. Muto, K. Ochiai, Y. Kimura et al., “Bach2 represses plasma cell gene regulatory network in B cells to promote antibody class switch,” EMBO Journal, vol. 29, no. 23, pp. 4048–4061, 2010. View at Publisher · View at Google Scholar · View at Scopus
  77. S. L. Nutt, N. Taubenheim, J. Hasbold, L. M. Corcoran, and P. D. Hodgkin, “The genetic network controlling plasma cell differentiation,” Seminars in Immunology, vol. 23, no. 5, pp. 341–349, 2011. View at Publisher · View at Google Scholar · View at Scopus
  78. D. Allman and S. Pillai, “Peripheral B cell subsets,” Current Opinion in Immunology, vol. 20, no. 2, pp. 149–157, 2008. View at Publisher · View at Google Scholar · View at Scopus
  79. L. Belver, V. G. de Yébenes, and A. R. Ramiro, “MicroRNAs prevent the generation of autoreactive antibodies,” Immunity, vol. 33, no. 5, pp. 713–722, 2010. View at Publisher · View at Google Scholar · View at Scopus
  80. H. Xie, M. Ye, R. Feng, and T. Graf, “Stepwise reprogramming of B cells into macrophages,” Cell, vol. 117, no. 5, pp. 663–676, 2004. View at Publisher · View at Google Scholar · View at Scopus
  81. A. Di Tullio, T. P. Vu Manh, A. Schubert, R. Månsson, and T. Graf, “CCAAT/enhancer binding protein α (C/EBPα)-induced transdifferentiation of pre-B cells into macrophages involves no overt retrodifferentiation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 41, pp. 17016–17021, 2011. View at Publisher · View at Google Scholar · View at Scopus
  82. J. Rodríguez-Ubreva, L. Ciudad, D. Gómez-Cabrero et al., “Pre-B cell to macrophage transdifferentiation without significant promoter DNA methylation changes,” Nucleic Acids Research, vol. 40, no. 5, pp. 1954–1968, 2012. View at Publisher · View at Google Scholar · View at Scopus
  83. C. F. Pereira, R. Terranova, N. K. Ryan et al., “Heterokaryon-based reprogramming of human B lymphocytes for pluripotency requires Oct4 but not Sox2,” PLoS Genetics, vol. 4, no. 9, Article ID e1000170, 2008. View at Publisher · View at Google Scholar · View at Scopus
  84. C. F. Pereira, F. M. Piccolo, T. Tsubouchi et al., “ESCs require PRC2 to direct the successful reprogramming of differentiated cells toward pluripotency,” Cell Stem Cell, vol. 6, no. 6, pp. 547–556, 2010. View at Publisher · View at Google Scholar · View at Scopus