Abstract
In the course of normal development, cells rarely are able to revert from a differentiated state back to an embryonic state. However, techniques exist that allow this reversal to take place. In an experiment performed over 50 years ago, single cell nuclear transfer from somatic cells to enucleated eggs was able to yield successful development of cloned Xenopus laevis (Gurdon et al., Nature 182:64–65, 1958). Through somatic cell nuclear transfer (NT), several cell divisions occur before the onset of new gene transcription; moreover, new cell types and even organisms can be derived (Campbell et al., Nature 380:64–66, 1996). More recently, terminally differentiated cells could be induced to reprogram to a pluripotent, embryonic stem (ES) cell-like state via overexpression of a particular subset of transcription factors (TF) (Takahashi and Yamanaka, Cell 126:663–676, 2006). These induced pluripotent stem (iPS) cells can then be re-differentiated into various tissue types, including both somatic and germ cells. A possible advantage that somatic cell NT harbors over iPS is that factors present in the egg have been shown to directly remove silencing of genes via chromatin decondensation, removal of histone modifications, and activation of gene transcription prior to cell division. Therefore, an improved understanding of how the egg facilitates nuclear reprogramming by natural means may identify components that can be used for more efficient reprogramming by this and other means.
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References
Beyhan Z, Iager AE, Cibelli JB (2007) Interspecies nuclear transfer: implications for embryonic stem cell biology. Stem Cell 1:502–512
Boiani M, Gentile L, Gambles VV, Cavaleri F, Redi CA, Schöler HR (2005) Variable reprogramming of the pluripotent stem cell marker Oct4 in mouse clones: distinct developmental potentials in different culture environments. Stem Cells 23:1089–1104
Briggs R, King TJ (1952) Transplantation of living nuclei from blastula cells into enucleated frogs’ eggs. Proc Natl Acad Sci USA 38:455–463
Byrne JA, Simonsson S, Western PS, Gurdon JB (2003) Nuclei of adult mammalian somatic cells are directly reprogrammed to oct-4 stem cell gene expression by amphibian oocytes. Curr Biol 13:1206–1213
Campbell KH, McWhir J, Ritchie WA, Wilmut I (1996) Sheep cloned by nuclear transfer from a cultured cell line. Nature 380:64–66
Chen J, Liu J, Chen Y, Yang J, Chen J, Liu H, Zhao X, Mo K, Song H, Guo L, Chu S, Wang D, Ding K, Pei D (2011) Rational optimization of reprogramming culture conditions for the generation of induced pluripotent stem cells with ultra-high efficiency and fast kinetics. Cell Res 21:884–894
Dominko T, Mitalipova M, Haley B, Beyhan Z, Memili E, McKusick B, First NL (1999) Bovine oocyte cytoplasm supports development of embryos produced by nuclear transfer of somatic cell nuclei from various mammalian species. Biol Reprod 60:1496–1502
Egli D, Eggan K (2006) Nuclear transfer into mouse oocytes. JoVE. doi:10.3791/116
Egli D, Chen AE, Saphier G, Powers D, Alper M, Katz K, Berger B, Goland R, Leibel RL, Melton DA, Eggan K (2011) Impracticality of egg donor recruitment in the absence of compensation. Cell Stem Cell 9:293–294
Gao S (2002) Germinal vesicle material is essential for nucleus remodeling after nuclear transfer. Biol Reprod 67:928–934
Gore A, Li Z, Fung HL, Young JE, Agarwal S, Antosiewicz-Bourget J, Canto I, Giorgetti A, Israel MA, Kiskinis E, Lee JH, Loh YH, Manos PD, Montserrat N, Panopoulos AD, Ruiz S, Wilbert ML, Yu J, Kirkness EF, Izpisua Belmonte JC, Rossi DJ, Thomson JA, Eggan K, Daley GQ, Goldstein LS, Zhang K (2011) Somatic coding mutations in human induced pluripotent stem cells. Nature 471:63–67
Gurdon JB (1960) The developmental capacity of nuclei taken from differentiating endoderm cells of Xenopus laevis. J Embryol Exp Morphol 8:505–526
Gurdon JB, Elsdale TR, Fischberg M (1958) Sexually mature individuals of Xenopus laevis from the transplantation of single somatic nuclei. Nature 182:64–65
Hussein SM, Batada NN, Vuoristo S, Ching RW, Autio R, Närvä E, Ng S, Sourour M, Hämäläinen R, Olsson C, Lundin K, Mikkola M, Trokovic R, Peitz M, Brüstle O, Bazett-Jones DP, Alitalo K, Lahesmaa R, Nagy A, Otonkoski T (2011) Copy number variation and selection during reprogramming to pluripotency. Nature 471:58–62
Jullien J, Astrand C, Halley-Stott RP, Garrett N, Gurdon JB (2010) Characterization of somatic cell nuclear reprogramming by oocytes in which a linker histone is required for pluripotency gene reactivation. Proc Natl Acad Sci USA 107:5483–5488
Jullien J, Pasque V, Halley-Stott RP, Miyamoto K, Gurdon JB (2011) Mechanisms of nuclear reprogramming by eggs and oocytes: a deterministic process? Nat Rev Mol Cell Biol 22:453–459
Kim K, Doi A, Wen B, Ng K, Zhao R, Cahan P, Kim J, Aryee MJ, Ji H, Ehrlich LI, Yabuuchi A, Takeuchi A, Cunniff KC, Hongguang H, McKinney-Freeman S, Naveiras O, Yoon TJ, Irizarry RA, Jung N, Seita J, Hanna J, Murakami P, Jaenisch R, Weissleder R, Orkin SH, Weissman IL, Feinberg AP, Daley GQ (2010) Epigenetic memory in induced pluripotent stem cells. Nature 467:285–290
Lister R, Pelizzola M, Kida YS, Hawkins RD, Nery JR, Hon G, Antosiewicz-Bourget J, O’Malley R, Castanon R, Klugman S, Downes M, Yu R, Stewart R, Ren B, Thomson JA, Evans RM, Ecker JR (2011) Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature 471:68–73
Miyamoto K, Pasque V, Jullien J, Gurdon JB (2011) Nuclear actin polymerization is required for transcriptional reprogramming of Oct4 by oocytes. Genes Dev 25:946–958
Mizutani E, Yamagata K, Ono T, Akagi S, Geshi M, Wakayama T (2012) Abnormal chromosome segregation at early cleavage is a major cause of the full-term developmental failure of mouse clones. Dev Biol 364:56–65
Noggle S, Fung HL, Gore A, Martinez H, Satriani KC, Prosser R, Oum K, Paull D, Druckenmiller S, Freeby M, Greenberg E, Zhang K, Goland R, Sauer MV, Leibel RL, Egli D (2011) Human oocytes reprogram somatic cells to a pluripotent state. Nature 478:7075
Okita K, Matsumura Y, Sato Y, Okada A, Morizane A, Okamoto S, Hong H, Nakagawa M, Tanabe K, Tezuka K, Shibata T, Kunisada T, Takahashi M, Takahashi J, Saji H, Yamanaka S (2011) A more efficient method to generate integration-free human iPS cells. Nat Meth 8:409–412
Polo JM, Liu S, Figueroa ME, Kulalert W, Eminli S, Tan KY, Apostolou E, Stadtfeld M, Li Y, Shioda T, Natesan S, Wagers AJ, Melnick A, Evans T, Hochedlinger K (2010) Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells. Nat Biotechnol 28:848–855
Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676
Wang W, Yang J, Liu H, Lu D, Chen X, Zenonos Z, Campos LS, Rad R, Guo G, Zhang S, Bradley A, Liu P (2011) Rapid and efficient reprogramming of somatic cells to induced pluripotent stem cells by retinoic acid receptor gamma and liver receptor homolog 1. Proc Natl Acad Sci USA 45:18283–18288
Young MA, Larson DE, Sun CW, George DR, Ding L, Miller CA, Lin L, Pawlik KM, Chen K, Fan X, Schmidt H, Kalicki-Veizer J, Cook LL, Swift GW, Demeter RT, Wendl MC, Sands MS, Mardis ER, Wilson RK, Townes TM, Ley TJ (2012) Background mutations in parental cells account for most of the genetic heterogeneity of induced pluripotent stem cells. Cell Stem Cell 10:570582
Zhang G, Shang B, Yang P, Cao Z, Pan Y, Zhou Q (2012) Induced pluripotent stem cell consensus genes: implication for the risk of tumorigenesis and cancers in induced pluripotent stem cell therapy. Stem Cells Dev 21:955–964
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Wang, S., Gurdon, J.B. (2013). Therapeutic Somatic Cell Reprogramming by Nuclear Transfer. In: Gage, F., Christen, Y. (eds) Programmed Cells from Basic Neuroscience to Therapy. Research and Perspectives in Neurosciences, vol 20. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-36648-2_2
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DOI: https://doi.org/10.1007/978-3-642-36648-2_2
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