EMBRYONIC STEM CELLS/INDUCED PLURIPOTENT STEM CELLS Concise Review: The Sox2-Oct4 Connection: Critical Players in a Much Larger Interdependent Network Integrated at Multiple Levels
EMBRYONIC STEM CELLS/INDUCED PLURIPOTENT STEM CELLS Concise Review: The Sox2-Oct4 Connection: Critical Players in a Much Larger Interdependent Network Integrated at Multiple Levels
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发表时间：
2013
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通讯作者：
A. Rizzino
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作者：
A. Rizzino
自从10多年前发现转录因子Sox 2和Oct 4在胚胎发生过程中发挥关键作用以来，它们一直是干细胞生物学的主要焦点。早期的研究表明，这两种转录因子共同调节胚胎干细胞（ESC）自我更新和多能性所需的基因。令人惊讶的是，Oct 4或Sox 2水平的微小变化（两倍）诱导ESC分化。因此，ESC必须将这两种转录因子的水平维持在较窄的范围内。已经进行了全基因组结合研究和无偏蛋白质组筛选，以破译Oct 4和Sox 2在ESC转录电路中所起的复杂作用。总之，这些和其他研究提供了一个全面的理解的分子机制，维持ESC的自我更新和抑制其分化。重要的是，这些研究描绘了一幅图景，其中Oct 4和Sox 2是一个更大的相互依赖网络的一部分，该网络由许多转录因子组成，这些转录因子在多个功能水平上相互连接。STEM CELLS 2013;31：1033-1039潜在利益冲突的披露见本文结尾。
The transcription factors Sox2 and Oct4 have been a major focus of stem cell biology since the discovery, more than 10 years ago, that they play critical roles during embryogenesis. Early work established that these two transcription factors work together to regulate genes required for the selfrenewal and pluripotency of embryonic stem cells (ESC). Surprisingly, small changes ( twofold) in the levels of either Oct4 or Sox2 induce the differentiation of ESC. Consequently, ESC must maintain the levels of these two transcription factors within narrow limits. Genome-wide binding studies and unbiased proteomic screens have been conducted to decipher the complex roles played by Oct4 and Sox2 in the transcriptional circuitry of ESC. Together, these and other studies provide a comprehensive understanding of the molecular machinery that sustains the self-renewal of ESC and restrains their differentiation. Importantly, these studies paint a landscape in which Oct4 and Sox2 are part of a much larger interdependent network composed of many transcription factors that are interconnected at multiple levels of function. STEM CELLS 2013;31:1033–1039 Disclosure of potential conflicts of interest is found at the end of this article.