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Volume 42 Issue 12
Dec.  2015
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Article Navigation >  Journal of Genetics and Genomics  > 2015  >  42(12): 661-670

The Epigenetic Reprogramming Roadmap in Generation of iPSCs from Somatic Cells

doi: 10.1016/j.jgg.2015.10.001
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    Department of Biomedicine, Aarhus University, Aarhus C 8000, Denmark

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  • Corresponding author: E-mail address: alun@biomed.au.dk (Yonglun Luo)
  • Received Date: 2015-03-20
  • Accepted Date: 2015-10-15
  • Rev Recd Date: 2015-10-09
    • Available Online: 2015-10-23
  • Publish Date: 2015-12-20
    Abstract
  • Reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) is a comprehensive epigenetic process involving genome-wide modifications of histones and DNA methylation. This process is often incomplete, which subsequently affects iPSC reprograming, pluripotency, and differentiation capacity. Here, we review the epigenetic changes with a focus on histone modification (methylation and acetylation) and DNA modification (methylation) during iPSC induction. We look at changes in specific epigenetic signatures, aberrations and epigenetic memory during reprogramming and small molecules influencing the epigenetic reprogramming of somatic cells. Finally, we discuss how to improve iPSC generation and pluripotency through epigenetic manipulations.
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  • [1]
    Ang, Y.S., Tsai, S.Y., Lee, D.F. et al. Cell, 145 (2011),pp. 183-197
    [2]
    Anokye-Danso, F., Trivedi, C.M., Juhr, D. et al. Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency Cell Stem Cell, 8 (2011),pp. 376-388
    [3]
    Apostolou, E., Hochedlinger, K. Chromatin dynamics during cellular reprogramming Nature, 502 (2013),pp. 462-471
    [4]
    Araki, R., Hoki, Y., Uda, M. et al. Crucial role of c-Myc in the generation of induced pluripotent stem cells Stem Cells, 29 (2011),pp. 1362-1370
    [5]
    Bar-Nur, O., Russ, H.A., Efrat, S. et al. Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells Cell Stem Cell, 9 (2011),pp. 17-23
    [6]
    Bock, C., Kiskinis, E., Verstappen, G. et al. Reference maps of human ES and iPS cell variation enable high-throughput characterization of pluripotent cell lines Cell, 144 (2011),pp. 439-452
    [7]
    Borooah, S., Phillips, M.J., Bilican, B. et al. Using human induced pluripotent stem cells to treat retinal disease Prog. Retin. Eye Res., 37 (2013),pp. 163-181
    [8]
    Brevini, T.A., Pennarossa, G., Rahman, M.M. et al. Morphological and molecular changes of human granulosa cells exposed to 5-azacytidine and addressed toward muscular differentiation Stem Cell Rev., 10 (2014),pp. 633-642
    [9]
    Chen, J., Gao, Y., Huang, H. et al. The combination of Tet1 with Oct4 generates high-quality mouse-induced pluripotent stem cells Stem Cells, 33 (2015),pp. 686-698
    [10]
    Chen, J., Han, Q., Pei, D. EMT and MET as paradigms for cell fate switching J. Mol. Cell Biol., 4 (2012),pp. 66-69
    [11]
    Chen, J., Liu, H., Liu, J. et al. H3K9 methylation is a barrier during somatic cell reprogramming into iPSCs Nat. Genet., 45 (2013),pp. 34-42
    [12]
    Chen, L.W., Kuang, F., Wei, L.C. et al. Potential application of induced pluripotent stem cells in cell replacement therapy for Parkinson's disease CNS Neurol. Disord. Drug Targets, 10 (2011),pp. 449-458
    [13]
    Chen, T., Dent, S.Y. Chromatin modifiers and remodellers: regulators of cellular differentiation Nat. Rev. Genet., 15 (2014),pp. 93-106
    [14]
    Christensen, B.C., Houseman, E.A., Marsit, C.J. et al. Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context PLoS Genet., 5 (2009),p. e1000602
    [15]
    Clapier, C.R., Cairns, B.R. The biology of chromatin remodeling complexes Annu. Rev. Biochem., 78 (2009),pp. 273-304
    [16]
    Delgado-Olguin, P., Recillas-Targa, F. Chromatin structure of pluripotent stem cells and induced pluripotent stem cells Brief Funct. Genom., 10 (2011),pp. 37-49
    [17]
    Ding, X., Wang, X., Sontag, S. et al. The polycomb protein Ezh2 impacts on induced pluripotent stem cell generation Stem Cells Dev., 23 (2014),pp. 931-940
    [18]
    English, K., Wood, K.J. Immunogenicity of embryonic stem cell-derived progenitors after transplantation Curr. Opin. Organ Transplant., 16 (2011),pp. 90-95
    [19]
    Esteban, M.A., Wang, T., Qin, B. et al. Vitamin C enhances the generation of mouse and human induced pluripotent stem cells Cell Stem Cell, 6 (2010),pp. 71-79
    [20]
    Faravelli, I., Riboldi, G., Nizzardo, M. et al. Stem cell transplantation for amyotrophic lateral sclerosis: therapeutic potential and perspectives on clinical translation Cell. Mol. Life Sci., 71 (2014),pp. 3257-3268
    [21]
    Federation, A.J., Bradner, J.E., Meissner, A. The use of small molecules in somatic-cell reprogramming Trends Cell Biol., 24 (2014),pp. 179-187
    [22]
    Galli, L.M., Munji, R.N., Chapman, S.C. et al. Frizzled10 mediates WNT1 and WNT3A signaling in the dorsal spinal cord of the developing chick embryo Dev. Dyn., 243 (2014),pp. 833-843
    [23]
    Hawkins, R.D., Hon, G.C., Lee, L.K. et al. Distinct epigenomic landscapes of pluripotent and lineage-committed human cells Cell Stem Cell, 6 (2010),pp. 479-491
    [24]
    He, J., Kallin, E.M., Tsukada, Y. et al. The H3K36 demethylase Jhdm1b/Kdm2b regulates cell proliferation and senescence through p15(Ink4b) Nat. Struct. Mol. Biol., 15 (2008),pp. 1169-1175
    [25]
    Heyn, H., Moran, S., Hernando-Herraez, I. et al. DNA methylation contributes to natural human variation Genome Res., 23 (2013),pp. 1363-1372
    [26]
    Hou, P., Li, Y., Zhang, X. et al. Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds Science, 341 (2013),pp. 651-654
    [27]
    Hu, K. All roads lead to induced pluripotent stem cells: the technologies of iPSC generation Stem Cells Dev., 23 (2014),pp. 1285-1300
    [28]
    Huangfu, D., Osafune, K., Maehr, R. et al. Nat. Biotechnol., 26 (2008),pp. 1269-1275
    [29]
    Huo, J.S., Zambidis, E.T. Pivots of pluripotency: the roles of non-coding RNA in regulating embryonic and induced pluripotent stem cells Biochim. Biophys. Acta, 1830 (2013),pp. 2385-2394
    [30]
    Iglesias-Garcia, O., Pelacho, B., Prosper, F. Induced pluripotent stem cells as a new strategy for cardiac regeneration and disease modeling J. Mol. Cell. Cardiol., 62 (2013),pp. 43-50
    [31]
    Im, H., Park, C., Feng, Q. et al. Dynamic regulation of histone H3 methylated at lysine 79 within a tissue-specific chromatin domain J. Biol. Chem., 278 (2003),pp. 18346-18352
    [32]
    Jia, W., Chen, W., Kang, J. The functions of microRNAs and long non-coding RNAs in embryonic and induced pluripotent stem cells Genom. Proteom. Bioinform., 11 (2013),pp. 275-283
    [33]
    Kang, R., Luo, Y., Zou, L. et al. Osteogenesis of human induced pluripotent stem cells derived mesenchymal stem cells on hydroxyapatite contained nanofibers RSC Adv., 4 (2014),pp. 5734-5739
    [34]
    Kang, R., Zhou, Y., Tan, S. et al. Mesenchymal stem cells derived from human induced pluripotent stem cells retain adequate osteogenicity and chondrogenicity but less adipogenicity Stem Cell Res. Ther., 6 (2015),p. 144
    [35]
    Keogh, M.C., Kurdistani, S.K., Morris, S.A. et al. Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex Cell, 123 (2005),pp. 593-605
    [36]
    Kim, K., Doi, A., Wen, B. et al. Epigenetic memory in induced pluripotent stem cells Nature, 467 (2010),pp. 285-290
    [37]
    Kim, K., Zhao, R., Doi, A. et al. Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells Nat. Biotechnol., 29 (2011),pp. 1117-1119
    [38]
    Kim, T.O., Park, J., Kang, M.J. et al. DNA hypermethylation of a selective gene panel as a risk marker for colon cancer in patients with ulcerative colitis Int. J. Mol. Med., 31 (2013),pp. 1255-1261
    [39]
    Koche, R.P., Smith, Z.D., Adli, M. et al. Reprogramming factor expression initiates widespread targeted chromatin remodeling Cell Stem Cell, 8 (2011),pp. 96-105
    [40]
    Lee, J., Xia, Y., Son, M.Y. et al. A novel small molecule facilitates the reprogramming of human somatic cells into a pluripotent state and supports the maintenance of an undifferentiated state of human pluripotent stem cells Angew. Chem. Int. Ed. Engl., 51 (2012),pp. 12509-12513
    [41]
    Li, H., Collado, M., Villasante, A. et al. Nature, 460 (2009),pp. 1136-1139
    [42]
    Li, W., Zhou, H., Abujarour, R. et al. Generation of human-induced pluripotent stem cells in the absence of exogenous Sox2 Stem Cells, 27 (2009),pp. 2992-3000
    [43]
    Liang, G., He, J., Zhang, Y. Kdm2b promotes induced pluripotent stem cell generation by facilitating gene activation early in reprogramming Nat. Cell Biol., 14 (2012),pp. 457-466
    [44]
    Liang, G., Zhang, Y. Genetic and epigenetic variations in iPSCs: potential causes and implications for application Cell Stem Cell, 13 (2013),pp. 149-159
    [45]
    Lin, T., Ambasudhan, R., Yuan, X. et al. A chemical platform for improved induction of human iPSCs Nat. Methods, 6 (2009),pp. 805-808
    [46]
    Lister, R., Pelizzola, M., Kida, Y.S. et al. Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells Nature, 471 (2011),pp. 68-73
    [47]
    Loewer, S., Cabili, M.N., Guttman, M. et al. Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells Nat. Genet., 42 (2010),pp. 1113-1117
    [48]
    Ma, H., Morey, R., O'Neil, R.C. et al. Abnormalities in human pluripotent cells due to reprogramming mechanisms Nature, 511 (2014),pp. 177-183
    [49]
    Maherali, N., Sridharan, R., Xie, W. et al. Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution Cell Stem Cell, 1 (2007),pp. 55-70
    [50]
    Mali, P., Chou, B.K., Yen, J. et al. Butyrate greatly enhances derivation of human induced pluripotent stem cells by promoting epigenetic remodeling and the expression of pluripotency-associated genes Stem Cells, 28 (2010),pp. 713-720
    [51]
    Mali, P., Ye, Z., Hommond, H.H. et al. Improved efficiency and pace of generating induced pluripotent stem cells from human adult and fetal fibroblasts Stem Cells, 26 (2008),pp. 1998-2005
    [52]
    Mattout, A., Biran, A., Meshorer, E. Global epigenetic changes during somatic cell reprogramming to iPS cells J. Mol. Cell Biol., 3 (2011),pp. 341-350
    [53]
    Minor, E.A., Court, B.L., Young, J.I. et al. Ascorbate induces ten-eleven translocation (Tet) methylcytosine dioxygenase-mediated generation of 5-hydroxymethylcytosine J. Biol. Chem., 288 (2013),pp. 13669-13674
    [54]
    Montserrat, N., Nivet, E., Sancho-Martinez, I. et al. Reprogramming of human fibroblasts to pluripotency with lineage specifiers Cell Stem Cell, 13 (2013),pp. 341-350
    [55]
    Morris, S.A., Daley, G.Q. A blueprint for engineering cell fate: current technologies to reprogram cell identity Cell Res., 23 (2013),pp. 33-48
    [56]
    Narlikar, G.J., Sundaramoorthy, R., Owen-Hughes, T. Mechanisms and functions of ATP-dependent chromatin-remodeling enzymes Cell, 154 (2013),pp. 490-503
    [57]
    Nazor, K.L., Altun, G., Lynch, C. et al. Recurrent variations in DNA methylation in human pluripotent stem cells and their differentiated derivatives Cell Stem Cell, 10 (2012),pp. 620-634
    [58]
    Nishino, K., Toyoda, M., Yamazaki-Inoue, M. et al. DNA methylation dynamics in human induced pluripotent stem cells over time PLoS Genet., 7 (2011),p. e1002085
    [59]
    Nishino, K., Toyoda, M., Yamazaki-Inoue, M. et al. Defining hypo-methylated regions of stem cell-specific promoters in human iPS cells derived from extra-embryonic amnions and lung fibroblasts PLoS One, 5 (2010),p. e13017
    [60]
    Nissenbaum, J., Bar-Nur, O., Ben-David, E. et al. Global indiscriminate methylation in cell-specific gene promoters following reprogramming into human induced pluripotent stem cells Stem Cell Rep., 1 (2013),pp. 509-517
    [61]
    Okita, K., Ichisaka, T., Yamanaka, S. Generation of germline-competent induced pluripotent stem cells Nature, 448 (2007),pp. 313-317
    [62]
    Okita, K., Nakagawa, M., Hyenjong, H. et al. Generation of mouse induced pluripotent stem cells without viral vectors Science, 322 (2008),pp. 949-953
    [63]
    Onder, T.T., Kara, N., Cherry, A. et al. Chromatin-modifying enzymes as modulators of reprogramming Nature, 483 (2012),pp. 598-602
    [64]
    Pawlak, M., Jaenisch, R. Genes Dev., 25 (2011),pp. 1035-1040
    [65]
    Peitz, M., Jungverdorben, J., Brustle, O. Disease-specific iPS cell models in neuroscience Curr. Mol. Med., 13 (2013),pp. 832-841
    [66]
    Pennarossa, G., Maffei, S., Campagnol, M. et al. Reprogramming of pig dermal fibroblast into insulin secreting cells by a brief exposure to 5-aza-cytidine Stem Cell Rev., 10 (2014),pp. 31-43
    [67]
    Pennarossa, G., Maffei, S., Campagnol, M. et al. Brief demethylation step allows the conversion of adult human skin fibroblasts into insulin-secreting cells Proc. Natl. Acad. Sci. USA, 110 (2013),pp. 8948-8953
    [68]
    Polo, J.M., Anderssen, E., Walsh, R.M. et al. A molecular roadmap of reprogramming somatic cells into iPS cells Cell, 151 (2012),pp. 1617-1632
    [69]
    Radzisheuskaya, A., Silva, J.C. Do all roads lead to Oct4? The emerging concepts of induced pluripotency Trends Cell Biol., 24 (2014),pp. 275-284
    [70]
    Rao, R.A., Dhele, N., Cheemadan, S. et al. Ezh2 mediated H3K27me3 activity facilitates somatic transition during human pluripotent reprogramming Sci. Rep., 5 (2015),p. 8229
    [71]
    Rosa, A., Brivanlou, A.H. Regulatory non-coding RNAs in pluripotent stem cells Int. J. Mol. Sci., 14 (2013),pp. 14346-14373
    [72]
    Rouhani, F., Kumasaka, N., de Brito, M.C. et al. Genetic background drives transcriptional variation in human induced pluripotent stem cells PLoS Genet., 10 (2014),p. e1004432
    [73]
    Ruiz, S., Diep, D., Gore, A. et al. Identification of a specific reprogramming-associated epigenetic signature in human induced pluripotent stem cells Proc. Natl. Acad. Sci. USA, 109 (2012),pp. 16196-16201
    [74]
    Sanchez-Freire, V., Lee, A.S., Hu, S. et al. Effect of human donor cell source on differentiation and function of cardiac induced pluripotent stem cells J. Am. Coll. Cardiol., 64 (2014),pp. 436-448
    [75]
    Schroeder, I.S. Potential of pluripotent stem cells for diabetes therapy Curr. Diab. Rep., 12 (2012),pp. 490-498
    [76]
    Shan, Z.Y., Wu, Y.S., Li, X. et al. Continuous passages accelerate the reprogramming of mouse induced pluripotent stem cells Cell Reprogram, 16 (2014),pp. 77-83
    [77]
    Shinagawa, T., Takagi, T., Tsukamoto, D. et al. Histone variants enriched in oocytes enhance reprogramming to induced pluripotent stem cells Cell Stem Cell, 14 (2014),pp. 217-227
    [78]
    Soufi, A., Donahue, G., Zaret, K.S. Facilitators and impediments of the pluripotency reprogramming factors' initial engagement with the genome Cell, 151 (2012),pp. 994-1004
    [79]
    Stadtfeld, M., Apostolou, E., Ferrari, F. et al. Ascorbic acid prevents loss of Dlk1-Dio3 imprinting and facilitates generation of all-iPS cell mice from terminally differentiated B cells Nat. Genet., 44 (2012),pp. 398-405
    [80]
    Stadtfeld, M., Nagaya, M., Utikal, J. et al. Induced pluripotent stem cells generated without viral integration Science, 322 (2008),pp. 945-949
    [81]
    Tachibana, M., Amato, P., Sparman, M. et al. Human embryonic stem cells derived by somatic cell nuclear transfer Cell, 153 (2013),pp. 1228-1238
    [82]
    Tahiliani, M., Koh, K.P., Shen, Y. et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1 Science, 324 (2009),pp. 930-935
    [83]
    Takahashi, K., Tanabe, K., Ohnuki, M. et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors Cell, 131 (2007),pp. 861-872
    [84]
    Takahashi, K., Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors Cell, 126 (2006),pp. 663-676
    [85]
    Taylor, S.M., Jones, P.A. Multiple new phenotypes induced in 10T1/2 and 3T3 cells treated with 5-azacytidine Cell, 17 (1979),pp. 771-779
    [86]
    Terasaki, H., Saitoh, T., Shiokawa, K. et al. Frizzled-10, up-regulated in primary colorectal cancer, is a positive regulator of the WNT–beta-catenin–TCF signaling pathway Int. J. Mol. Med., 9 (2002),pp. 107-112
    [87]
    Thomson, J.A., Itskovitz-Eldor, J., Shapiro, S.S. et al. Embryonic stem cell lines derived from human blastocysts Science, 282 (1998),pp. 1145-1147
    [88]
    Unternaehrer, J.J., Daley, G.Q. Induced pluripotent stem cells for modelling human diseases Philos. Trans. R. Soc. Lond. B Biol. Sci., 366 (2011),pp. 2274-2285
    [89]
    Wang, T., Chen, K., Zeng, X. et al. The histone demethylases Jhdm1a/1b enhance somatic cell reprogramming in a vitamin-C-dependent manner Cell Stem Cell, 9 (2011),pp. 575-587
    [90]
    Wang, T., Wu, H., Li, Y. et al. Subtelomeric hotspots of aberrant 5-hydroxymethylcytosine-mediated epigenetic modifications during reprogramming to pluripotency Nat. Cell Biol., 15 (2013),pp. 700-711
    [91]
    Wu, T., Liu, Y., Wen, D. et al. Histone variant H2A.X deposition pattern serves as a functional epigenetic mark for distinguishing the developmental potentials of iPSCs Cell Stem Cell, 15 (2014),pp. 281-294
    [92]
    Xu, H., Yi, B.A., Wu, H. et al. Highly efficient derivation of ventricular cardiomyocytes from induced pluripotent stem cells with a distinct epigenetic signature Cell Res., 22 (2012),pp. 142-154
    [93]
    Yehezkel, S., Rebibo-Sabbah, A., Segev, Y. et al. Reprogramming of telomeric regions during the generation of human induced pluripotent stem cells and subsequent differentiation into fibroblast-like derivatives Epigenetics, 6 (2011),pp. 63-75
    [94]
    Yu, J., Vodyanik, M.A., Smuga-Otto, K. et al. Induced pluripotent stem cell lines derived from human somatic cells Science, 318 (2007),pp. 1917-1920
    [95]
    Zhang, L., Deng, L., Chen, F. et al. Inhibition of histone H3K79 methylation selectively inhibits proliferation, self-renewal and metastatic potential of breast cancer Oncotarget, 5 (2014),pp. 10665-10677
    [96]
    Zhang, Z., Gao, Y., Gordon, A. et al. PLoS One, 6 (2011),p. e26592
    [97]
    Zhang, Z., Wu, W.S. Sodium butyrate promotes generation of human induced pluripotent stem cells through induction of the miR302/367 cluster Stem Cells Dev., 22 (2013),pp. 2268-2277
    [98]
    Zhou, Y., Kim, J., Yuan, X. et al. Epigenetic modifications of stem cells: a paradigm for the control of cardiac progenitor cells Circ. Res., 109 (2011),pp. 1067-1081
    [99]
    Zou, L., Luo, Y., Chen, M. et al. A simple method for deriving functional MSCs and applied for osteogenesis in 3D scaffolds Sci. Rep., 3 (2013),p. 2243
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