Epigenetic Reprogramming Induced Pluripotency

Anna Meiliana, Andi Wijaya


BACKGROUND: The ability to reprogram mature cells to an embryonic-like state by nuclear transfer or by inducing the expression of key transcription factors has provided us with critical opportunities to linearly map the epigenetic parameters that are essential for attaining pluripotency.

CONTENT: Epigenetic reprogramming describes a switch in gene expression of one kind of cell to that of another unrelated cell type. Early studies in frog cloning provided some of the first experimental evidence for reprogramming. Subsequent procedures included mammalian somatic cell nuclear transfer, cell fusion, induction of pluripotency by ectopic gene expression, and direct reprogramming. Through these methods it becomes possible to derive one kind of specialized cell (such as a brain cell) from another, more accessible tissue, such as skin in the same individual. This has potential applications for cell replacement without the immunosuppression treatments commonly required when cells are transferred between genetically different individuals.

SUMMARY: Reprogramming with transcription factors offers tremendous promise for the future development of patient-specific pluripotent cells and for studies of human disease. The identification of optimized protocols for the differentiation of iPS cells and ES cells into multiple functional cell types in vitro and their proper engraftment in vivo will be challenged in the coming years. Given that the first small molecule approaches aimed at activating pluripotency genes have already been devised and that murine iPS cells have recently been derived by using non-integrative transient expression strategies of the reprogramming factors, we expect that human iPS cells without permanent genetic alterations will soon be generated.

KEYWORDS: epigenetics, reprogramming, pluripotency, stem cells, iPS cells, chromatin, DNA methylation

Full Text:



Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH. Nature. Viable offspring derived from fetal and adult mammalian cells. 1997; 385: 810-3, CrossRef.

Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007; 131: 861-72, CrossRef.

Cibelli J, Kiessling AA, Cunniff K, Richards C, Lanza RP, West MD. Rapid Communication: Somatic cell nuclear transfer in humans: Pronuclear and early embryonic development. J Regen Med. 2004; 2: 25-31, CrossRef.

Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007; 318: 1917-20, CrossRef.

Park IH, Zhao R, West JA, Yabuuchi A, Huo H, Ince TA, et al. Reprogramming of human somatic cells to pluripotency with defined factors. Nature. 2008; 451: 141-6, CrossRef.

Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T, et al. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nature Biotechnol. 2008; 26: 101-6, CrossRef.

Ohm JE, Baylin SB. Stem cell epigenetics. In: Turksen K, editors. Stem Cell Biology and Regenerative Medicine. New York: Humana Press; 2009. p.235-46, CrossRef.

Jakson-Grusby L. DNA methylation and the epigenetic program in stem cells. In: Turksen K, editors. Stem Cell Biology and Regenerative Medicine. New York: Humana Press; 2009. p.277-84, CrossRef.

Kangaspeska S, Stride B, Métivier R, Polycarpou-Schwarz M, Ibberson D, Carmouche RP, et al. Transient cyclical methylation of promoter DNA. Nature. 2008; 452: 112-5, CrossRef.

Métivier R, Gallais R, Tiffoche C, Le Péron C, Jurkowska RZ, Carmouche RP, et al. Cyclical DNA methylation of a transcriptionally active promoter. Nature. 2008; 452: 45-50, CrossRef.

Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009; 324: 930-5, CrossRef.

Bird A. Perceptions of epigenetics. Nature. 2007; 447: 396-8, CrossRef.

Suzuki M, Bird A. DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet. 2008; 9: 465-76, CrossRef.

Murrell a, Rakyan VK, Beck S. From genome to epigenome. Hum Mol Genet. 2005; 14: R3-10, CrossRef.

Ng RK, Gurdon JB. Epigenetic inheritance of cell differentiation status. Cell Cycle. 2008; 7: 1173-7, CrossRef.

Zhang TY, Meaney MJ. Epigenetics and the environmental regulation of the genome and its function. Annu Rev Psychol. 2010; 61: 439-66, CrossRef.

Youngson NA, Whitelaw E. Transgenerational epigenetic effects. Annu Rev Genomics Hum Genet. 2008; 9: 233-57, CrossRef.

Bernstein BE, Meissner A, Lander ES. The mammalian epigenome. Cell. 2007; 128: 669-81, CrossRef.

Satterlee JS, Schubeler D, Ng HH. Tackling the epigenome: challenges and opportunities for collaboration. Nat Biotechnol. 2010; 28: 1039-44, CrossRef.

Haberland M, Montgomery RL, Olson EN. The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat Rev Genet. 2009; 10: 32-42, CrossRef.

Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002; 16: 6-21, CrossRef.

Jaenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet. 2003; 33 (Suppl 3): 245-54, CrossRef.

Yamanaka S. Strategies and new developments in the generation of patient-specific pluripotent stem cells. Cell Stem Cell. 2007; 1: 39-49, CrossRef.

Meissner A. Epigenetic modifications in pluripotent and differentiated cells. Nat Biotechnol 2010; 28: 1079-88, CrossRef.

Horn PJ, Peterson CL. Molecular biology: Chromatin higher order folding-wrapping up transcription. Science. 2002; 297: 1824-7, CrossRef.

Kiefer JC. Epigenetics in development. Dev Dyn. 2007; 236: 1144-56, CrossRef.

Thyagarajan B, Rao M. Role of DNA methylation and epigenetics in stem cells. In: Turksen K, editors. Regulatory Networks in Stem Cells, Stem Cell Biology and Regenerative Medicine. New York: Humana Press; 2009. p.269-76, CrossRef.

Portella A, Esteller M. Epigenetic modifications and human disease. Nat Biotechnol. 2010; 28: 1056-68, CrossRef.

Esteller, M. Epigenetics in evolution and disease. Lancet. 2008; 372: S90-6, CrossRef.

Kacem S, Feil R. Chromatin mechanisms in genomic imprinting. Mamm Genome. 2009; 20: 544-56, CrossRef.

Esteller, M. Epigenetic gene silencing in cancer: the DNA hypermethylome. Hum Mol Genet. 2007; 16: R50-9, CrossRef.

Lopez-Serra L, Esteller M. Proteins that bind methylated DNA and human cancer: reading the wrong words. Br J Cancer. 2008; 98: 1881-5, CrossRef.

Kuroda A, Rauch TA, Todorov I, Ku HT, Al-Abdullah IH, Kandeel F, et al. Insulin gene expression is regulated by DNA methylation. PLoS ONE. 2009; 4: e6953, CrossRef.

Kouzarides T. Chromatin modifications and their function. Cell. 2007; 128: 693-705, CrossRef.

Daujat S, Zeissler U, waldmann T, Happel N, Schneider R. HP1 binds specifically to Lys26-methylated histone H1.4, whereas simultaneous Ser27 phosphorylation blocks HP1 binding. J Biol Chem. 2005; 280: 38090-5, CrossRef.

Rando OJ, Chang HY. Genome-wide views of chromatin structure. Annu Rev Biochem. 2009; 78: 245-71, CrossRef.

Huertas D, Sendra R, Munoz P. Chromatin dynamics coupled to DNA repair. Epigenetics. 2009; 4: 31-42, CrossRef.

Luco RF, Pan Q, Tominaga K, Blencowe BJ, Pereira-Smith OM, Misteli T. Regulation of alternative splicing by histone modifications. Science. 2010; 327: 996-1000, CrossRef.

Chodavarapu RK, Feng S, Bernatavichute YV, Chen PY, Stroud H, Yu Y, et al. Relationship between nucleosome positioning and DNA methylation. Nature. 2010; 466: 388-92, CrossRef.

Getun IV, Wu ZK, Khalil AM, Bois PR. Nucleosome occupancy landscape and dynamics at mouse recombination hotspots. EMBO Rep. 2010; 11: 555-60, CrossRef.

Berger SL, Kouzarides T, Shiekhattar R, Shilatifard A. An operational definition of epigenetics. Genes Dev. 2009; 23: 781-3, CrossRef.

Ptashne M. On the use of the word 'epigenetic'. Curr Biol. 2007; 17: R233-6, CrossRef.

Skipper M, Weiss U, Gray N. Plasticity. Nature. 2010; 465: 703, CrossRef.

Pera MF, Tam PPL. Extrinsic regulation of pluripotent stem cells. Nature. 2010; 465: 713-20, CrossRef.

Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science 1998; 282: 1145-7, CrossRef.

Reubinoff BE, Pera MF, Fong CY, Trounson A, Bongso, A. Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nature Biotechnol. 2000; 18: 399-404, CrossRef.

Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126: 663-76, CrossRef.

Lander AD. The ‘stem cell’ concept: is it holding us back? J Biol. 2009; 8: 70, CrossRef.

Tam PP, Loebel DA. Gene function in mouse embryogenesis: get set for gastrulation. Nat Rev Genet. 2007; 8: 368-81, CrossRef.

Murry CE, Keller G. Differentiation of embryonic stem cells to clinically relevant populations: lessons from embryonic development. Cell. 2008; 132: 661-80, CrossRef.

Rossant J, Tam PP. Blastocyst lineage formation, early embryonic asymmetries and axis patterning in the mouse. Development. 2009; 136: 701-13, CrossRef.

Dulac C. Brain function and chromatin plasticity. Nature. 2010; 465: 728-35, CrossRef.

Meshorer E, Yellajoshula D, George E, Scambler PJ, Brown DT, Misteli T. Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells. Developmental Cell. 2006; 10: 105-16, CrossRef.

Azuara V, Perry P, Sauer S, et al. Chromatin signatures of pluripotent cell lines. Nat Cell Biol. 2006; 8: 532-8, CrossRef.

Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J, et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell. 2006; 125: 315-26, CrossRef.

Abu-Remaileh M, Bergman Y. Epigenetic signature of embryonal stem cells: A DNA methylation perspective. Regulatory Networks in Stem Cells, Stem Cell Biology and Regenerative Medicine. New York: Humana Press; 2009. p.247-56, CrossRef.

Laurent L, Wong E, Li G, Huynh T, Tsirigos A, Ong CT, et al. Dynamic changes in the human methylome during differentiation. Genome Res. 2010; 20: 320-31, CrossRef.

Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 2009; 462: 315-22, CrossRef.

Meissner A, Mikkelsen TS, Gu H, Wernig M, Hanna J, Sivachenko A, et al. Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature. 2008; 454: 766-70, CrossRef.

Faust C, Lawson KA, Schork NJ, Thiel B, Magnuson T. The polycomb-group gene eed is required for normal morphogenetic movements during gastrulation in the mouse embryo. Development. 1998; 125: 4495-506, PMID.

Ku M, Koche RP, Rheinbay E, Mendenhall EM, Endoh M, Mikkelsen TS, et al. Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains. Plos Genet. 2008; 4: e1000242, CrossRef.

Zhao XD, Han X, Chew JL, Liu J, Chiu KP, Choo A, et al. Wholegenome mapping of histone H3 Lys4 and 27 trimethylations reveals distinct genomic compartments in human embryonic stem cells. Cell Stem Cell. 2007; 1: 286-98, CrossRef.

Pan G, Tian S, Nie J, Yang C, Ruotti V, Wei H, et al. Wholegenome analysis of histone H3 lysine 4 and lysine 27 methylation in human embryonic stem cells. Cell Stem Cell. 2007; 1: 299-312, CrossRef.

Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, Giannoukos G, et al. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature. 2007; 448: 553-60, CrossRef.

Guenther MG, Levine SS, Boyer LA, Jaenisch R, Young RA. A chromatin landmark and transcription initiation at most promoters in human cells. Cell. 2007; 130: 77-88, CrossRef.

Heintzman ND, Stuart RK, Hon G, Fu Y, Ching CW, Hawkins R, et al. Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat Genet. 2007; 39: 311-8, CrossRef.

Efroni S, Duttagupta R, Cheng J, Dehghani H, Hoeppner DJ, Dash C, et al. Global transcription in pluripotent embryonic stem cells. Cell Stem Cell. 2008; 2, 437-47, CrossRef.

Gu H, Bock C, Mikkelsen TS, Jäger N, Smith ZD, Tomazou E, et al. Genome-scale DNA methylation mapping of clinical samples at single-nucleotide resolution. Nat Methods. 2010; 7: 133-6, CrossRef.

Goren A, Ozsolak F, Shoresh N, Ku M, Adli M, Hart C, et al. Chromatin profiling by directly sequencing small quantities ofimmunoprecipitated DNA. Nat Methods. 2010; 7: 47-9, CrossRef.

Bernstein BE, Stamatoyannopoulos JA, Costello JF, Ren B, Milosavljevic A, Meissner A, et al. The NIH roadmap epigenomics mapping consortium. Nat Biotechnol. 2010; 28: 1045-8, CrossRef.

Mohammad HP, Baylin SB. Linking cell signaling and the epigenetic machinery. Nat Biotechnol. 2010; 28: 1033-8, CrossRef.

Hemberger M, Dean W, Reik W. Epigenetic dynamics of stem cells and cell lineage commitment: digging Waddington's canal. Nat Rev Mol Cell Biol. 2009; 10: 526-37, CrossRef.

Hochedlinger K, Plath K. Epigenetic reprogramming and induced pluripotency. Development. 2009; 136: 509-23, CrossRef.

Zhou,Q, Melton DA. Extreme makeover: converting one cell into another. Cell Stem Cell. 2008; 3: 382-8, CrossRef.

Yamanaka S, Blau HM. Nuclear reprogramming to a pluripotent state by three approaches. Nature. 2010; 465: 704-12, CrossRef.

Athanasiadou R, de Sousa D, Myant K, Merusi C, Stancheva I, Bird A. Targeting of de novo DNA methylation throughout the Oct-4 gene regulatory region in differentiating embryonic stem cells. PLoS ONE. 2010; 5: e9937, CrossRef.

Feldman N, Gerson A, Fang J, Li E, Zhang Y, Shinkai Y, et al. G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis. Nat Cell Biol. 2006; 8: 188-94, CrossRef.

Epsztejn-Litman S, Feldman N, Abu-Remaileh M, Shufaro Y, Gerson A, Ueda J, et al. De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes. Nat Struct Mol Biol. 2008; 15: 1176-83, CrossRef.

Li JY, Pu MT, Hirasawa R, Li BZ, Huang YN, Zeng R, et al. Synergistic function of DNA methyltransferases Dnmt3a and Dnmt3b in the methylation of Oct4 and Nanog. Mol Cell Biol. 2007; 27: 8748-59, CrossRef.

Bhutani N, Brady JJ, Damian M, Sacco A, Corbel SY, Blau HM. Reprogramming towards pluripotency requires AID-dependent DNA demethylation. Nature. 2010; 463: 1042-7, CrossRef.

Ito S, D'Alessio AC, Taranova OV, Hong K, Sowers LC, Zhang Y. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature. 2010; 466: 1129-33, CrossRef.

Sridharan R, Tchieu J, Mason MJ, Yachechko R, Kuoy E, Horvath S, et al. Role of the murine reprogramming factors in the induction of pluripotency. Cell. 2009; 136: 364-77, CrossRef.

Lee TI, Jenner RG, Boyer LA, Guenther MG, Levine SS, Kumar RM, et al. Control of developmental regulators by Polycomb in human embryonic stem cells. Cell. 2006; 125: 301-13, CrossRef.

Marson A, Foreman R, Chevalier B, Bilodeau S, Kahn M, Young RA, et al. Wnt signaling promotes reprogramming of somatic cells to pluripotency. Cell Stem Cell. 2008; 3: 132-5, CrossRef.

Xu RH, Sampsell-Barron TL, Gu F, Root S, Peck RM, Pan G, et al. NANOG is a direct target of TGFbeta/activin-mediated SMAD signaling in human ESCs. Cell Stem Cell. 2008; 3: 196-206, CrossRef.

Conti L, Pollard SM, Gorba T, Reitano E, Toselli M, Biella G, et al. Niche-independent symmetrical self-renewal of a mammalian tissue stem cell. PLoS Biol. 2005; 3: e283, CrossRef.

Brüstle O, Jones KN, Learish RD, Karram K, Choudhary K, Wiestler OD, et al. Embryonic stem cell-derived glial precursors: a source of myelinating transplants. Science. 1999; 285: 754-6, CrossRef.

Niwa H, Burdon T, Chambers I, Smith, A. Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3. Genes Dev. 1998; 12: 2048-60, CrossRef.

Niwa H, Ogawa K, Shimosato D, Adachi, K. A parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells. Nature. 2009; 460: 118-22, CrossRef.

Hirabayashi Y, Itoh Y, Tabata H, Nakajima K, Akiyama T, Masuyama N, et al. The Wnt/beta-catenin pathway directs neuronal differentiation of cortical neural precursor cells. Development. 2004; 131: 2791-801, CrossRef.

Gunhaga L, Marklund M, Sjödal M, Hsieh JC, Jessell TM, Edlund T. Specification of dorsal telencephalic character by sequential Wnt and FGF signaling. Nat Neurosci. 2003; 6: 701-7, CrossRef.

Machon O, van den Bout CJ, Backman M, Kemler R, Krauss S. Role of beta-catenin in the developing cortical and hippocampal neuroepithelium. Neuroscience. 2003; 122: 129-43, CrossRef.

Backman M, Machon O, Mygland L, van den Bout CJ, Zhong W, Taketo MM, et al. Effects of canonical Wnt signaling on dorso-ventral specification of the mouse telencephalon. Dev Biol. 2005; 279: 155-68, CrossRef.

Maden M. Retinoic acid in the development, regeneration and maintenance of the nervous system. Nat Rev Neurosci. 2007; 8: 755-65, CrossRef.

Andrews PW. Retinoic acid induces neuronal differentiation of a cloned human embryonal carcinoma cell line in vitro. Dev Biol. 1984; 103: 285-93, CrossRef.

Bertrand N, Dahmane N. Sonic hedgehog signaling in forebrain development and its interactions with pathways that modify its effects. Trends Cell Biol. 2006; 16: 597-605, CrossRef.

Jenuwein T, Allis CD. Translating the histone code. Science. 2001; 293: 1074-80, CrossRef.

Richly H, Lange M, Simboeck E, Di Croce, L. Setting and resetting of epigenetic marks in malignant transformation and development. Bioessays. 2010; 32: 669-79, CrossRef.

Klose RJ, Yan Q, Tothova Z, Yamane K, Erdjument-Bromage H, Tempst P, et al. The retinoblastoma binding protein RBP2 is an H3K4 demethylase. Cell. 2007; 128: 889-900, CrossRef.

Pasini D, Hansen KH, Christensen J, Agger K, Cloos PA, Helin K. Coordinated regulation of transcriptional repression by the RBP2 H3K4 demethylase and polycomb-repressive complex 2. Genes Dev. 2008; 22: 1345-55, CrossRef.

Borggrefe T, Oswald F. Cell. Mol. The Notch signaling pathway: transcriptional regulation at Notch target genes. Life Sci. 2009; 66: 1631-1646, CrossRef.

Lin CH, Jackson AL, Guo J, Linsley PS, Eisenman RN. Myc-regulated microRNAs attenuate embryonic stem cell differentiation. EMBO J. 2009; 28: 3157-70, CrossRef.

Dang CV. Micro-managing and restraining pluripotent stem cells by MYC. EMBO J. 2009; 28: 3065-6, CrossRef.

Voog J, Jones DL. Stem cells and the niche: a dynamic duo. Cell Stem Cell. 2010; 6: 103-15, CrossRef.

Eggan K, Baldwin K, Tackett M, Osborn, J, Gogos J, Chess A, et al. Mice cloned from olfactory sensory neurons. Nature. 2004; 428: 44-9, CrossRef.

Hochedlinger K, Jaenisch R. Monoclonal mice generated by nuclear transfer from mature B and T donor cells. Nature. 2002; 415: 1035-8, CrossRef.

Li J, Ishii T, Feinstein P, Mombaerts P. Odorant receptor gene choice is reset by nuclear transfer from mouse olfactory sensory neurons. Nature. 2004; 428: 393-9, CrossRef.

Matsui Y, Zsebo K, Hogan BL. Derivation of pluripotential embryonic stem cells from murine primordial germ cells in culture. Cell. 1992; 70: 841-7, CrossRef.

Resnick JL, Bixler LS, Cheng L, Donovan PJ. Long-term proliferation of mouse primordial germ cells in culture. Nature. 1992; 359: 550-1, CrossRef.

Xie H, Ye M, Feng R, Graf T. Stepwise reprogramming of B cells into macrophages. Cell. 2004; 117: 663-76, CrossRef.

Davis RL, Weintraub H, Lassar AB. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell. 1987; 51: 987-1000, CrossRef.

Jaenisch R, Young R. Stem cells, the molecular circuitry ofpluripotency and nuclear reprogramming. Cell. 2008; 132: 567-82, CrossRef.

Maherali N, Ahfeldt T, Rigamonti A, Utikal J, Cowan C, Hochedlinger, K. A high-efficiency system for the generation and study of human induced pluripotent stem cells. Cell Stem Cell. 2008; 3: 340-5, CrossRef.

Mikkelsen TS, Hanna J, Zhang X, Ku M, Wernig M, Schorderet P, et al. Dissecting direct reprogramming through integrative genomic analysis. Nature. 2008; 454: 49-55, CrossRef.

Okita K, Ichisaka T,Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature. 2007; 448: 313-7, CrossRef.

Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K, et al. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature. 2007; 448: 318-24, CrossRef.

Hanna J, Markoulaki S, Schorderet P, Carey BW, Beard C, Wernig M, et al. Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. 2008; Cell. 133: 250-64, CrossRef.

Kim JB, Zaehres H, Wu G, Gentile L, Ko K, Sebastiano V, et al. Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature. 2008; 454: 646-50, CrossRef.

Viswanathan SR, Daley GQ, Gregory RI. Selective blockade of microRNA processing by Lin28. Science. 2008; 320: 97-100, CrossRef.

Chang HH, Hemberg M, Barahona M, Ingber DE, Huang S. Transcriptome-wide noise controls lineage choice in mammalian progenitor cells. Nature. 2008; 453: 544-7, CrossRef.

Huangfu D, Maehr R, Guo W, Eijkelenboom A, Snitow M, Chen AE, et al. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol. 2008; 26: 795-7, CrossRef.

Huangfu D, Osafune K, Maehr R, Guo W, Eijkelenboom A, Chen S, et al. Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat Biotechnol. 2008; 26: 1269-75, CrossRef.

Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, et al. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell. 2005; 122: 947-56, CrossRef.

Dominguez-Sola D, Ying CY, Grandori C, Ruggiero L, Chen B, Li M, Galloway DA, et al. Non-transcriptional control of DNA replication by c-Myc. Nature. 2007; 448: 445-51, CrossRef.

Knoepfler PS. Why myc? An unexpected ingredient in the stem cell cocktail. Cell Stem Cell. 2008; 2, 18-21, CrossRef.

Lanza RP, Cibelli JB, West MD: Prospects for the use of nuclear transfer in human transplantation. Nat Biotechnol. 1999; 17: 1171-4, CrossRef.

Lanza RP, Cibelli JB, West MD. Human therapeutic cloning. Nat Med. 1999; 5: 975-7, CrossRef.

Scholer HR. Octamania: the POU factors in murine development. Trends Genet. 1991; 7: 323-9, CrossRef.

Herr W, Cleary MA. The POU domain: versatility in transcriptional regulation by a flexible two-in-one DNA-binding domain. Genes Dev. 1995; 9: 1679-93, CrossRef.

Nichols J, Zevnik B, Anastassiadis K, Niwa H, Klewe-Nebenius D, Chambers I, et al. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell. 1998; 95: 379-91, CrossRef.

Niwa H, Miyazaki J, Smith AG. Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet. 2000; 24: 37372-6, CrossRef.

Chambers I, Colby D, Robertson M, et al. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell. 2003; 113: 643-55, CrossRef.

Mitsui K, Tokuzawa Y, Itoh H, et al. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell. 2003; 113: 631-42, CrossRef.

Darr H, Mayshar Y, Benvenisty N. Overexpression of NANOG in human ES cells enables feeder-free growth while inducing primitive ectoderm features. Development. 2006; 133: 1193-1201, CrossRef.

Avilion AA, Nicolis SK, Pevny LH, Perez L, Vivian N, Lovell-Badge R. Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev. 2003; 17: 126-40, CrossRef.

Wood HB, Episkopou V. Comparative expression of the mouse Sox1, Sox2 and Sox3 genes from pre-gastrulation to early somite stages. Mech Dev. 1999; 86: 197-201, CrossRef.

Rowland BD, Peeper DS. KLF4, p21 and context-dependent opposing forces in cancer. Nat Rev Cancer. 2006; 6: 11-23, CrossRef.

Knoepfler PS. Myc goes global: new tricks for an old oncogene. Cancer Res. 2007; 67: 5061-3, CrossRef.

Li Y, McClintick J, Zhong L, Edenberg HJ, Yoder MC, Chan RJ. Murine embryonic stem cell differentiation is promoted by SOCS-3 and inhibited by the zinc finger transcription factor Klf4. Blood. 2005; 105: 635-7, CrossRef.

Cartwright P, McLean C, Sheppard A, Rivett D, Jones K, Dalton S. LIF/STAT3 controls ES cell self-renewal and pluripotency by a Myc-dependent mechanism. Development. 2005; 132: 885-96, CrossRef.

Loh YH, Zhang W, Chen X, George J, Ng HH. Jmjd1a and Jmjd2c histone H3 Lys 9 demethylases regulate self-renewal in embryonic stem cells. Genes Dev. 2007; 21: 2545-57, CrossRef.

Richards M, Tan SP, Tan JH, Chan WK, Bongso A. The transcriptome profile of human embryonic stem cells as defined by SAGE. Stem Cells. 2004; 22: 51-64, CrossRef.

Gurdon JB. From nuclear transfer to nuclear reprogramming: the reversal of cell differentiation. Annu Rev Cell Dev Biol. 2006; 22: 1-22, CrossRef.

Tada M, Takahama Y, Abe K, Nakatsuji N, Tada T. Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells. Curr Biol. 2001; 11: 1553-8, CrossRef.

Surani MA, Hayashi K, Hajkova P. Genetic and epigenetic regulators of pluripotency. Cell. 2007; 128: 747-62, CrossRef.

Aoi T, Yae K, Nakagawa M, Ichisaka T, Okita K, Takahashi K, et al. Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science. 2008; 321: 699-702, CrossRef.

Stadtfeld M, Brennand K, Hochedlinger, K. Reprogramming of pancreatic beta cells into induced pluripotent stem cells. Curr Biol. 2008; 18: 890-894, CrossRef.

Yamanaka, S. Elite and stochastic models for induced pluripotent stem cell generation. Nature. 2009; 460: 49-52, CrossRef.

Kim JB, Sebastiano V, Wu G, Araúzo-Bravo MJ, Sasse P, Gentile L, et al. Oct4-induced pluripotency in adult neural stem cells. Cell. 2009; 136: 411-9, CrossRef.

Graf T, Enver T. Forcing cells to change lineages. Nature. 2009; 462: 587-94, CrossRef.

Yechoor V, Liu V, Espiritu C, Paul A, Oka K, Kojima H, et al. Neurogenin 3 is sufficient for transdetermination of hepatic progenitor cells into neo-islets in vivo but not transdifferentiation of hepatocytes. Dev Cell. 2009; 16: 358-73, CrossRef.

Zhou Q,Brown J,Kanarek A, Rajagopal J, Melton DA. In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature. 2008; 455: 627-32, CrossRef.

DOI: https://doi.org/10.18585/inabj.v3i2.139

Indexed by:






The Prodia Education and Research Institute