ESCs (Embryonic Stem Cells) are Pluripotent cells capable of differentiating into any cell type of the body. Only three species of Mammals have yielded long-term cultures of self-renewing ESCs- Mice, Monkeys, and Humans. Human ESCs are derived from Blastocysts, multicellular structures originating from four cleavages of fertilized oocytes. Isolated from the ICM (Inner Cell Mass) of Blastocysts, the ESCs retain properties of self-renewal and the potential to be committed and to differentiate toward most cell lineages. They are able to spontaneously give rise to different progenies of the three embryonic layers, namely, the Ectoderm, the Mesoderm and the Endoderm. The Pluripotency of ESCs has attracted great attention for their potential use in tissue and cell therapy. However, the molecular and developmental mechanisms controlling Pluripotency and Differentiation of ESCs are largely unknown. Human ESC Pluripotency is regulated by a combination of Extrinsic and Intrinsic factors. Unlike Mouse, Extrinsic factor LIF (Leukemia Inhibitory Factor) is not sufficient to maintain Human ESC and BMPs (Bone Morphogenic Proteins) cause rapid differentiation. Instead, FGF (Fibroblast Growth Factor) signaling and a balance between TGF-Beta (Transforming Growth Factor-Beta) /Activin and BMP signaling are central to the self-renewal of Human ESCs. Intrinsic factors regulating Pluripotency in Human ESCs include a battery of transcription factors including Oct4 (Octamer Binding Transcription Factor-4), SOX2 (SRY (Sex Determining Region-Y) Box-2) and Nanog (Ref.1 & 2).
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1.Embryonic stem cells.
Biswas A, Hutchins R. Stem Cells Dev. 2007 Apr;16(2):213-22. 2.Human embryonic stem cells: the battle between self-renewal and differentiation. Darr H, Benvenisty N. Regen Med. 2006 May;1(3):317-25. 3.Activin A maintains self-renewal and regulates fibroblast growth factor, Wnt, and bone morphogenic protein pathways in human embryonic stem cells. Xiao L, Yuan X, Sharkis SJ. Stem Cells. 2006 Jun;24(6):1476-86. 4.Expression of nodal, lefty-a, and lefty-B in undifferentiated human embryonic stem cells requires activation of Smad2/3. Besser D. J Biol Chem. 2004 Oct 22;279(43):45076-84. 5.TGFbeta/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells. James D, Levine AJ, Besser D, Hemmati-Brivanlou A. Development. 2005 Mar;132(6):1273-82. 6.BMPs regulate differentiation of a putative visceral endoderm layer within human embryonic stem-cell-derived embryoid bodies. Conley BJ, Ellis S, Gulluyan L, Mollard R. Biochem Cell Biol. 2007 Feb;85(1):121-32. 7.Noggin and bFGF cooperate to maintain the pluripotency of human embryonic stem cells in the absence of feeder layers. Wang G, Zhang H, Zhao Y, Li J, Cai J, Wang P, Meng S, Feng J, Miao C, Ding M, Li D, Deng H. Biochem Biophys Res Commun. 2005 May 13;330(3):934-42. 8.Basic FGF and suppression of BMP signaling sustain undifferentiated proliferation of human ES cells. Xu RH, Peck RM, Li DS, Feng X, Ludwig T, Thomson JA. Nat Methods. 2005 Mar;2(3):185-90. 9.Wnt/beta-catenin/CBP signaling maintains long-term murine embryonic stem cell pluripotency. Miyabayashi T, Teo JL, Yamamoto M, McMillan M, Nguyen C, Kahn M. Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5668-73. 10.Wnt3a regulates survival, expansion, and maintenance of neural progenitors derived from human embryonic stem cells. Davidson KC, Jamshidi P, Daly R, Hearn MT, Pera MF, Dottori M. Mol Cell Neurosci. 2007 Aug 7; 11.Development of serum-free culture systems for human embryonic stem cells. Chase LG, Firpo MT. Curr Opin Chem Biol. 2007 Aug;11(4):367-72. 12.Essential roles of sphingosine-1-phosphate and platelet-derived growth factor in the maintenance of human embryonic stem cells. Pébay A1, Wong RC, Pitson SM, Wolvetang EJ, Peh GS, Filipczyk A, Koh KL, Tellis I, Nguyen LT, Pera MF. Stem Cells. 2005 Nov-Dec;23(10):1541-8. Epub 2005 Aug 4. 13.Analysis of Oct4-dependent transcriptional networks regulating self-renewal and pluripotency in human embryonic stem cells. Babaie Y, Herwig R, Greber B, Brink TC, Wruck W, Groth D, Lehrach H, Burdon T, Adjaye J. Stem Cells. 2007 Feb;25(2):500-10. 14.A protein interaction network for pluripotency of embryonic stem cells. Wang J, Rao S, Chu J, Shen X, Levasseur DN, Theunissen TW, Orkin SH. Nature. 2006 Nov 16;444(7117):364-8. Epub 2006 Nov 8. 15.A UTF1-based selection system for stable homogeneously pluripotent human embryonic stem cell cultures. Tan SM, Wang ST, Hentze H, Droge P. Nucleic Acids Res. 2007 Sep 12; 16.Nanog and transcriptional networks in embryonic stem cell pluripotency. Pan G, Thomson JA. Cell Res. 2007 Jan;17(1):42-9. 17.NANOG maintains self-renewal of primate ES cells in the absence of a feeder layer. Yasuda SY, Tsuneyoshi N, Sumi T, Hasegawa K, Tada T, Nakatsuji N, Suemori H. Genes Cells. 2006 Sep;11(9):1115-23. 18.Core transcriptional regulatory circuitry in human embryonic stem cells. Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, Gifford DK, Melton DA, Jaenisch R, Young RA. Cell. 2005 Sep 23;122(6):947-56.
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