Molecular mechanisms on embryonic stem cell pluripotency

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1 Chinese Bulletin of Life Sciences Vol. 19, No. 4 Aug., (2007) (ES ) ES LIF BMP4 Wnt Oct4 Nanog Sox2 FoxD3 ES ES ES Q813 A Molecular mechanisms on embryonic stem cell pluripotency PAN Guangjin, PEI Duanqing* (Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou , China) Abstract: Derived from early embryo, embryonic stem (ES) cells have potential to self renew indefinitely and develop to any type of cells in human body (pluripotency). Several extrinsic signals such as LIF, BMPs and Wnt can support the self-renewal and pluripotency of embryonic stem (ES) cells through regulating the pluripotent genes. In combination with intrinsic transcription factors such as FoxD3, Nanog, Oct4, these factors form a regulatory network to support or limit each other s expression level, which maintain the properties of ES cells. Key words: embryonic stem cells; self-renewal; differentiation (ES ) (blastocyst) (ICM) [1-3] ICM ES [2-4] ES ES ES ES [5] ES ES ES ES ES (1974 ) (1965 ), * pei_duanqing@gibh.ac.cn

2 373 ES ES ES (1)ES (self-renewal) (2) (3) ES ES 1 ES 1.1 LIF STAT3 LIF STAT3 LIF LIF IL-6 LIF gp130 JAKs JAKs LIF gp130 gp130 STATs STAT3 STAT3 STAT3 [6-7] LIF ES LIF ES LIF [8-9] LIF STAT3 ES Niwa [10] ES STAT3 STAT3 LIF ES STAT3 ES [10] 1.2 BMP4 ES ES LIF ES LIF LIF ES LIF ES Ying [11] BMP4 LIF ES LIF BMP4 ES ES ES BMP4 TGF-β SMAD ES BMP4 ID ES ID BMP4 LIF ES Qi [12] BMP4 ES p38mapk [12] 1.3 Wnt ES LIF BMP4 ES ES LIF [13] Wnt ES ES [13-14] GSK Wnt Wnt GSK (Bio) ES GSK Wnt ES ES rex1 oct4 nanog Bio 2 ES ES Oct4 Nanog FoxD3 SoxD3, LIF STAT3 [15-16] ICM Epiblast ES EC( ) 2.1 Oct4 ES Oct4(

3 374 Oct3) homeodomain POU(Pit-Oct-Unc), AGTCAAAT (octamer motif) Oct4 ES Oct4 Oct4 Oct4 [17-19] Oct4 [20] Oct4 ES Oct4 Niwa [21] Oct4 ES Oct4 Oct4 50% ES (primitive endoderm) Oct4 50% ES (trophoblast) Oct4 ES Oct4 Oct4 352 POU domain N domain C domain POU domain DNA N domain (proline) [22] C domain Brehm [23] Oct4 C domain DNA POU DNA DNA Gal4 Oct4 POU domain Oct4 Oct4 Liu [25-26] Oct4 hcg hcg Oct4 IFN IFN Ets-2 Yamamoto [27] Oct4 Ets-2 Ets-2 IFN Oct4 Oct4 Oct4 [28-32] FGF-4 3' Oct4 Sox2 FGF4 [28-29] UTF1 [32] Oct4 [33-36] Oct4 Oct4 ES 2.2 Nanog ES Nanog ES [37-38] Oct4 Nanog Nanog (murola) ICM Northern blot Nanog [37] Nanog ES (primitive endodern) [38] Nanog (epiblast) ES

4 Homeobox Nanog ES LIF-STAT3 Nanog ES LIF ES ES [37-38] LIF Nanog ES STAT3 STAT3 Nanog ES LIF-STAT3-Oct4 ES Oct4 ES Nanog [38] ES Oct4 ES Oct4 Nanog ES Mitsui [37] SELEX Nanog Gata6 Nanog ES Nanog 2.3 ES Oct4 Nanog FoxD3 FoxD3 (epiblast) Nanog [5] FoxD3 ES Guo [6] FoxD3 Oct4 Nanog FoxD3 [7-11], ES 1-1 ES ES 3 Oct4 Nanog Oct4 Oct4 ICM(ES ) Oct4 Nanog ICM Oct4 ICM Nanog ICM (epiblast) (Endoderm Mesoderm Ectoderm) Nanog ICM (hypoblast) Oct4 Nanog Sox2 FoxD3 (after implantation) ES LIF ES LIF ES STAT3 STAT3 ES ES Oct4 ES ES Oct4 ES ES ES Nanog ES ES LIF ES ( Gata-4 Gata-6) ES (primitive endoderm) 1 ES Oct4 Nanog FoxD3 STAT3

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