ZFX controls the self-renewal of human embryonic stem cells.
ZFX controls the self-renewal of human embryonic stem cells.
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DOI：
10.1371/journal.pone.0042302
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Tomishima MJ
中科院分区：
文献类型：
--
作者：
Harel S;Tu EY;Weisberg S;Esquilin M;Chambers SM;Liu B;Carson CT;Studer L;Reizis B;Tomishima MJ
胚胎干细胞（ESC）和诱导多能干细胞（iPSC）由于其无限的自我更新和广泛的分化能力，在再生医学和疾病建模中提供了巨大的希望。有证据表明，小鼠和人类胚胎干细胞的生长特性和关键信号通路不同;因此，进行功能研究以测试物种之间多能干细胞自我更新的保守机制是至关重要的。以前，我们确定了转录因子Zfx作为一个关键的调节自我更新的小鼠胚胎干细胞。在这里，我们将这些发现扩展到人类ESC。在hESC中ZFX敲低阻碍了克隆生长，并在连续重新接种后降低了集落大小。ZFX过表达增强克隆形成在Y-27632的存在下，在低密度下增加集落大小，并降低人胚胎干细胞中分化相关基因的表达。ZFX过表达的hESC抵抗自发分化，但当提供适当的提示时，可以定向分化为内胚层和神经细胞。因此，ZFX作为一个分子变阻器调节hESC自我更新和分化之间的平衡，揭示了在小鼠和人类ESC的自我更新机制的密切进化保守。
Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) offer great promise in regenerative medicine and disease modeling due to their unlimited self-renewal and broad differentiation capacity. There is evidence that the growth properties and critical signaling pathways differ between murine and human ESCs; therefore, it is essential to perform functional studies to test the putatively conserved mechanisms of pluripotent stem cell self-renewal between species. Previously, we identified the transcription factor Zfx as a key regulator of self-renewal in murine ESCs. Here we extend those findings to human ESCs. ZFX knockdown in hESCs hindered clonal growth and decreased colony size after serial replating. ZFX overexpression enhanced clone formation in the presence of Y-27632, increased colony size at low density and decreased expression of differentiation-related genes in human ESCs. ZFX-overexpressing hESCs resisted spontaneous differentiation but could be directed to differentiate into endodermal and neural cell fates when provided with the appropriate cues. Thus, ZFX acts as a molecular rheostat regulating the balance between self-renewal and differentiation in hESCs, revealing the close evolutionary conservation of the self-renewal mechanisms in murine and human ESCs.
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影响因子：
64.8
作者：
Brons, I. Gabrielle M.;Smithers, Lucy E.;Vallier, Ludovic
通讯作者：
Vallier, Ludovic
DOI：
10.1073/pnas.0404700101
发表时间：
2004-08-24
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
56.9
作者：
Thomson, JA;Itskovitz-Eldor, J;Jones, JM
通讯作者：
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