干细胞维持多能状态的奥妙（附原文）

托斯卡纳教父

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! D1 p- T  x9 h$ z) fRegulation of stem cell pluripotency and differentiation involves a mutual regulatory circuit of the Nanog, OCT4 and SOX2 pluripotency transcription factors with Polycomb Repressive Complexes and Stem Cell micro-RNAs.# H. O7 G  D8 u+ i( L" k% A$ V

& g. F* {( m6 N' n9 oRegulation of stem cell pluripotency and differentiation involves a mutual regulatory circuit of the Nanog, OCT4 and SOX2 pluripotency transcription factors with Polycomb Repressive Complexes and Stem Cell micro-RNAs.9 p1 b# K3 `( U: o$ k

: g9 ~9 _2 }* Z7 |Stem Cells Dev. 2009 May 29;
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Authors: Kashyap V, Rezende NC, Scotland KB, Shaffer SM, Persson JL, Gudas LJ, Mongan NP
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. r0 ^# ]) ]! R' v6 DCoordinated transcription-factor networks have emerged as the master regulatory mechanisms of stem cell pluripotency and differentiation. Many stem cell specific transcription factors, including the pluripotency transcription factors, OCT4, Nanog and SOX2 function in combinatorial complexes to regulate the expression of loci which are involved in ES pluripotency and cellular differentiation. This review will address how these pathways form a reciprocal regulatory circuit whereby the equilibrium between stem cell self renewal, proliferation and differentiation is in perpetual balance. We will discuss how distinct epigenetic repressive pathways involving polycomb complexes, DNA methylation, and microRNAs cooperate to reduce transcriptional noise and to prevent stochastic and aberrant induction of differentiation. We will provide a brief overview of how these networks cooperate to modulate differentiation along hematopoietic and neuronal lineages. Finally, we will describe how aberrant functioning of components of the stem cell regulatory network may contribute to malignant transformation of adult stem cells and the establishment of a "cancer stem cell" phenotype and thereby underlie multiple types of human malignancies.) K( g& g6 V" h# _0 Q1 v
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