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Noncell Autonomous Reprogramming to a Pluripotent State

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Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

Abstract

In 2006, Takahashi and Yamanaka discovered that somatic cells could be reprogrammed to a pluripotent state by the expression of a defined set of exogenous transcription factors. This represents a significant breakthrough for the practical use of stem cells in regenerative medicine. Since then, several strategies have been used to generate induced pluripotent (iPS) cells that include nucleic acid and nonnucleic acid-based approaches, with and without epigenetic modifications. The purpose of these different approaches for generating iPS cells, besides understanding the ­underlying mechanism, is to develop a facile method for reprogramming without genetic alteration, suitable for clinical use. Here, we discuss different strategies for generating iPS cells, with an emphasis on a recent noncell autonomous approach to reprogram somatic progenitors that regenerate cornea to a pluripotent state through the recruitment of endogenous transcription factors.

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References

  • Aasen T, Raya A, Barrero MJ et al (2008) Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nat Biotechnol 26:1276–1284

    Article  PubMed  CAS  Google Scholar 

  • Balasubramanian S, Babai N, Chaudhuri A et al (2009) Non cell-autonomous reprogramming of adult ocular progenitors: generation of pluripotent stem cells without exogenous transcription factors. Stem Cells 27:3053–3062

    PubMed  CAS  Google Scholar 

  • Basta G, Racanicchi L, Mancuso F et al (2004) Transdifferentiation molecular pathways of neonatal pig pancreatic duct cells into endocrine cell phenotypes. Transplant Proc 36:2857–2863

    Article  PubMed  CAS  Google Scholar 

  • Blelloch R, Venere M, Yen J et al (2007) Generation of induced pluripotent stem cells in the absence of drug selection. Cell Stem Cell 1:245–247

    Article  PubMed  CAS  Google Scholar 

  • Brambrink T, Foreman R, Welstead GG et al (2008) Sequential expression of pluripotency markers during direct reprogramming of mouse somatic cells. Cell Stem Cell 2:151–159

    Article  PubMed  CAS  Google Scholar 

  • Briggs R, King TJ (1952) Transplantation of living nuclei from blastula cells into enucleated frogs’ eggs. Proc Natl Acad Sci USA 38:455–463

    Article  PubMed  CAS  Google Scholar 

  • Conboy IM, Conboy MJ, Wagers AJ et al (2005) Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature 433:760–764

    Article  PubMed  CAS  Google Scholar 

  • Cowan CA, Atienza J, Melton DA et al (2005) Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science 309:1369–1373

    Article  PubMed  CAS  Google Scholar 

  • Do JT, Scholer HR (2009) Regulatory circuits underlying pluripotency and reprogramming. Trends Pharmacol Sci 30:296–302

    Article  PubMed  CAS  Google Scholar 

  • Eminli S, Foudi A, Stadtfeld M et al (2009) Differentiation stage determines potential of hematopoietic cells for reprogramming into induced pluripotent stem cells. Nat Genet 41:968–976

    Article  PubMed  CAS  Google Scholar 

  • Esteban MA, Wang T, Qin B et al (2010) Vitamin C enhances the generation of mouse and human induced pluripotent stem cells. Cell Stem Cell 6:71–79

    Article  PubMed  CAS  Google Scholar 

  • Gurdon JB (1962) The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. J Embryol Exp Morphol 10:622–640

    PubMed  CAS  Google Scholar 

  • Hemmati-Brivanlou A, Melton D (1997) Vertebrate embryonic cells will become nerve cells unless told otherwise. Cell 88:13–17

    Article  PubMed  CAS  Google Scholar 

  • Hockemeyer D, Soldner F, Cook EG et al (2008) A drug-inducible system for direct reprogramming of human somatic cells to pluripotency. Cell Stem Cell 3:346–353

    Article  PubMed  CAS  Google Scholar 

  • Huangfu D, Maehr R, Guo W et al (2008a) Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol 26:795–797

    Article  PubMed  CAS  Google Scholar 

  • Huangfu D, Osafune K, Maehr R et al (2008b) Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat Biotechnol 26:1269–1275

    Article  PubMed  CAS  Google Scholar 

  • Jaenisch R, Young R (2008) Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell 132:567–582

    Article  PubMed  CAS  Google Scholar 

  • James J, Das AV, Bhattacharya S et al (2003) In vitro generation of early-born neurons from late retinal progenitors. J Neurosci 23:8193–8203

    PubMed  CAS  Google Scholar 

  • Kaji K, Norrby K, Paca A et al (2009) Virus-free induction of pluripotency and subsequent ­excision of reprogramming factors. Nature 458:771–775

    Article  PubMed  CAS  Google Scholar 

  • Kim D, Kim CH, Moon JI et al (2009a) Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 4:472–476

    Article  PubMed  CAS  Google Scholar 

  • Kim JB, Greber B, Arauzo-Bravo MJ et al (2009b) Direct reprogramming of human neural stem cells by OCT4. Nature 461:649–653

    Article  PubMed  CAS  Google Scholar 

  • Kimura H, Tada M, Nakatsuji N et al (2004) Histone code modifications on pluripotential nuclei of reprogrammed somatic cells. Mol Cell Biol 24:5710–5720

    Article  PubMed  CAS  Google Scholar 

  • Ko K, Tapia N, Wu G et al (2009) Induction of pluripotency in adult unipotent germline stem cells. Cell Stem Cell 5:87–96

    Article  PubMed  CAS  Google Scholar 

  • Kubicek S, O’Sullivan RJ, August EM et al (2007) Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol Cell 25:473–481

    Article  PubMed  CAS  Google Scholar 

  • Li X, Wei W, Yong J et al (2005a) The genetic heterozygosity and fitness of tetraploid embryos and embryonic stem cells are crucial parameters influencing survival of mice derived from embryonic stem cells by tetraploid embryo aggregation. Reproduction 130:53–59

    Article  PubMed  CAS  Google Scholar 

  • Li X, Yu Y, Wei W et al (2005b) Simple and efficient production of mice derived from embryonic stem cells aggregated with tetraploid embryos. Mol Reprod Dev 71:154–158

    Article  PubMed  CAS  Google Scholar 

  • Li W, Wei W, Zhu S et al (2009) Generation of rat and human induced pluripotent stem cells by combining genetic reprogramming and chemical inhibitors. Cell Stem Cell 4:16–19

    Article  PubMed  Google Scholar 

  • Longo L, Bygrave A, Grosveld FG et al (1997) The chromosome make-up of mouse embryonic stem cells is predictive of somatic and germ cell chimaerism. Transgenic Res 6:321–328

    Article  PubMed  CAS  Google Scholar 

  • Lowry WE, Plath K (2008) The many ways to make an iPS cell. Nat Biotechnol 26:1246–1248

    Article  PubMed  CAS  Google Scholar 

  • Maherali N, Hochedlinger K (2008) Guidelines and techniques for the generation of induced ­pluripotent stem cells. Cell Stem Cell 3:595–605

    Article  PubMed  CAS  Google Scholar 

  • Maherali N, Sridharan R, Xie W et al (2007) Directly reprogrammed fibroblasts show global ­epigenetic remodeling and widespread tissue contribution. Cell Stem Cell 1:55–70

    Article  PubMed  CAS  Google Scholar 

  • Maherali N, Ahfeldt T, Rigamonti A et al (2008) A high-efficiency system for the generation and study of human induced pluripotent stem cells. Cell Stem Cell 3:340–345

    Article  PubMed  CAS  Google Scholar 

  • Marson A, Levine SS, Cole MF et al (2008) Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells. Cell 134:521–533

    Article  PubMed  CAS  Google Scholar 

  • Martin GR (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA 78:7634–7638

    Article  PubMed  CAS  Google Scholar 

  • Mikkelsen TS, Hanna J, Zhang X et al (2008) Dissecting direct reprogramming through integrative genomic analysis. Nature 454:49–55

    Article  PubMed  CAS  Google Scholar 

  • Nagy A, Rossant J, Nagy R et al (1993) Derivation of completely cell culture-derived mice from early-passage embryonic stem cells. Proc Natl Acad Sci USA 90:8424–8428

    Article  PubMed  CAS  Google Scholar 

  • Ng F, Boucher S, Koh S et al (2008) PDGF, TGF-beta, and FGF signaling is important for ­differentiation and growth of mesenchymal stem cells (MSCs): transcriptional profiling can identify markers and signaling pathways important in differentiation of MSCs into adipogenic, chondrogenic, and osteogenic lineages. Blood 112:295–307

    Article  PubMed  CAS  Google Scholar 

  • Okita K, Ichisaka T, Yamanaka S (2007) Generation of germline-competent induced pluripotent stem cells. Nature 448:313–317

    Article  PubMed  CAS  Google Scholar 

  • Okita K, Nakagawa M, Hyenjong H et al (2008) Generation of mouse induced pluripotent stem cells without viral vectors. Science 322:949–953

    Article  PubMed  CAS  Google Scholar 

  • Pan RL, Chen Y, Xiang LX et al (2008) Fetal liver-conditioned medium induces hepatic specification from mouse bone marrow mesenchymal stromal cells: a novel strategy for hepatic transdifferentiation. Cytotherapy 10:668–675

    Article  PubMed  CAS  Google Scholar 

  • Park IH, Zhao R, West JA et al (2008) Reprogramming of human somatic cells to pluripotency with defined factors. Nature 451:141–146

    Article  PubMed  CAS  Google Scholar 

  • Shi Y, Desponts C, Do JT et al (2008a) Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds. Cell Stem Cell 3:568–574

    Article  PubMed  CAS  Google Scholar 

  • Shi Y, Do JT, Desponts C et al (2008b) A combined chemical and genetic approach for the ­generation of induced pluripotent stem cells. Cell Stem Cell 2:525–528

    Article  PubMed  CAS  Google Scholar 

  • Singh AM, Dalton S (2009) The cell cycle and Myc intersect with mechanisms that regulate ­pluripotency and reprogramming. Cell Stem Cell 5:141–149

    Article  PubMed  CAS  Google Scholar 

  • Smukler SR, Runciman SB, Xu S et al (2006) Embryonic stem cells assume a primitive neural stem cell fate in the absence of extrinsic influences. J Cell Biol 172:79–90

    Article  PubMed  CAS  Google Scholar 

  • Soldner F, Hockemeyer D, Beard C et al (2009) Parkinson’s disease patient-derived induced ­pluripotent stem cells free of viral reprogramming factors. Cell 136:964–977

    Article  PubMed  CAS  Google Scholar 

  • Stadtfeld M, Nagaya M, Utikal J et al (2008a) Induced pluripotent stem cells generated without viral integration. Science 322:945–949

    Article  PubMed  CAS  Google Scholar 

  • Stadtfeld M, Maherali N, Breault DT et al (2008b) Defining molecular cornerstones during ­fibroblast to iPS cell reprogramming in mouse. Cell Stem Cell 2:230–240

    Article  PubMed  CAS  Google Scholar 

  • Stadtfeld M, Apostolou E, Akutsu H et al (2010) Aberrant silencing of imprinted genes on ­chromosome 12qF1 in mouse induced pluripotent stem cells. Nature 465:175–181

    Article  PubMed  CAS  Google Scholar 

  • Sun N, Panetta NJ, Gupta DM et al (2009) Feeder-free derivation of induced pluripotent stem cells from adult human adipose stem cells. Proc Natl Acad Sci USA 106:15720–15725

    Article  PubMed  CAS  Google Scholar 

  • Tada M, Takahama Y, Abe K et al (2001) Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells. Curr Biol 11:1553–1558

    Article  PubMed  CAS  Google Scholar 

  • Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676

    Article  PubMed  CAS  Google Scholar 

  • Takahashi K, Okita K, Nakagawa M et al (2007a) Induction of pluripotent stem cells from ­fibroblast cultures. Nat Protoc 2:3081–3089

    Article  PubMed  CAS  Google Scholar 

  • Takahashi K, Tanabe K, Ohnuki M et al (2007b) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872

    Article  PubMed  CAS  Google Scholar 

  • Wernig M, Meissner A, Foreman R et al (2007) In vitro reprogramming of fibroblasts into a ­pluripotent ES-cell-like state. Nature 448:318–324

    Article  PubMed  CAS  Google Scholar 

  • Wernig M, Lengner CJ, Hanna J et al (2008) A drug-inducible transgenic system for direct ­reprogramming of multiple somatic cell types. Nat Biotechnol 26:916–924

    Article  PubMed  CAS  Google Scholar 

  • Wilmut I, Schnieke AE, McWhir J et al (1997) Viable offspring derived from fetal and adult ­mammalian cells. Nature 385:810–813

    Article  PubMed  CAS  Google Scholar 

  • Woltjen K, Michael IP, Mohseni P et al (2009) piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature 458:766–770

    Article  PubMed  CAS  Google Scholar 

  • Yang K, Jiang Z, Wang D et al (2009) Corneal epithelial-like transdifferentiation of hair follicle stem cells is mediated by pax6 and beta-catenin/Lef-1. Cell Biol Int 33:861–866

    Article  PubMed  CAS  Google Scholar 

  • Yu J, Vodyanik MA, Smuga-Otto K et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920

    Article  PubMed  CAS  Google Scholar 

  • Yusa K, Rad R, Takeda J et al (2009) Generation of transgene-free induced pluripotent mouse stem cells by the piggyBac transposon. Nat Meth 6:363–369

    Article  CAS  Google Scholar 

  • Zhao X, Das AV, Bhattacharya S et al (2008) Derivation of neurons with functional properties from adult limbal epithelium: implications in autologous cell therapy for photoreceptor degeneration. Stem Cells 26:939–949

    Article  PubMed  CAS  Google Scholar 

  • Zhou H, Wu S, Joo JY et al (2009) Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell 4:381–384

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Iqbal Ahmad .

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Parameswaran, S., Balasubramanian, S., Ahmad, I. (2011). Noncell Autonomous Reprogramming to a Pluripotent State. In: Ainscough, J., Yamanaka, S., Tada, T. (eds) Nuclear Reprogramming and Stem Cells. Stem Cell Biology and Regenerative Medicine. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-225-0_12

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