Sall4 Regulates Distinct Transcription Circuitries in Different Blastocyst-Derived Stem Cell Lineages
Sall4 Regulates Distinct Transcription Circuitries in Different Blastocyst-Derived Stem Cell Lineages
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DOI：
10.1016/j.stem.2008.08.004
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发表时间：
2008-11-06
期刊：
影响因子：
23.9
通讯作者：
Lim, Bing
中科院分区：
文献类型：
--
作者：
Lim, Chin Yan;Tam, Wai-Leong;Lim, Bing
干细胞在干细胞特异性转录程序的调控下进行自我更新或分化，每个转录因子协调一组特定基因的活动。在此我们证明，单个转录因子能够调节两种不同的源自囊胚的干细胞系——胚胎干细胞（ESCs）和胚外内胚层（XEN）细胞中不同的核心回路。转录因子Sall4对早期胚胎发育和胚胎干细胞的多能性是必需的。Sall4在XEN细胞中也有表达，Sall4的缺失会破坏自我更新并诱导分化。全基因组分析显示，Sall4在胚胎干细胞和XEN细胞中调节不同的基因集，并且在相应细胞类型中Sall4靶标的缺失会诱导分化。Sall4与Oct4、Sox2和Nanog在胚胎干细胞中形成一个关键的相互关联的自动调节网络。在XEN细胞中，Sall4调节关键的与XEN谱系相关的基因Gata4、Gata6、Sox7和Sox17。我们的研究结果表明了Sall4如何作为两种不同干细胞系的关键干性因子发挥作用。
Stem cells self-renew or differentiate under the governance of a stem-cell-specific transcriptional program, with each transcription factor orchestrating the activities of a particular set of genes. Here we demonstrate that a single transcription factor is able to regulate distinct core circuitries in two different blastocyst-derived stem cell lines, embryonic stem cells (ESCs) and extraembryonic endoderm (XEN) cells. The transcription factor Sall4 is required for early embryonic development and for ESC pluripotency. Sall4 is also expressed in XEN cells, and depletion of Sall4 disrupts self-renewal and induces differentiation. Genome-wide analysis reveals that Sall4 is regulating different gene sets in ESCs and XEN cells, and depletion of Sall4 targets in the respective cell types induces differentiation. With Oct4, Sox2, and Nanog, Sall4 forms a crucial interconnected autoregulatory network in ESCs. In XEN cells, Sall4 regulates the key XEN lineage-associated genes Gata4, Gata6, Sox7, and Sox17. Our findings demonstrate how Sall4 functions as an essential sternness factor for two different stem cell lines.