Delayed differentiation in embryonic stem cells and mesodermal progenitors in the absence of CtBP2.

Delayed differentiation in embryonic stem cells and mesodermal progenitors in the absence of CtBP2.
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DOI:
10.1016/j.mod.2009.10.002
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发表时间:
2010-01
影响因子:
2.6
通讯作者:
Lemischka, Ihor R.
Lemischka, Ihor R.
中科院分区:
生物学4区
文献类型:
--
作者:
Tarleton, Heather P.;Lemischka, Ihor R.

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哺乳动物胚胎干细胞 (ESC) 的特点是能够自我更新并产生三个胚层。 ESC 是众多原始祖细胞和定向谱系的多能来源,可以做出导致不对称或对称细胞分裂的化学计量决策。一些基因已被确定为维持自我更新所必需的,但很少有非谱系特异性基因被确定为分化所必需的。我们从微阵列数据中选择了染色质因子 Ctbp2,因为与定型祖细胞相比,它在干细胞中表达丰富。 RNA 干扰 (RNAi) 用于敲低小鼠 ESC 中的基因表达,并在 ESC 和中胚层测定中评估转导细胞自我更新和分化的潜力。在这里,我们使用体外系统证明了 Ctbp2 在干细胞维持和分化调节中的重要作用。 Ctbp2 的敲低增加了培养物中 ESC 的患病率,延迟了 LIF 撤除诱导的分化,并引入了中胚层分化的发育变化。提出了一个模型来说明 Ctbp2 在维持自我更新和分化决策平衡方面的重要性。
Mammalian embryonic stem cells (ESCs) are characterized by an ability to self-renew and give rise to each of the three germ layers. ESCs are a pluripotential source of numerous primitive progenitors and committed lineages and can make stoichiometric decisions leading to either asymmetric or symmetric cell division. Several genes have been identified as essential for maintenance of self-renewal, but few non-lineage specific genes have been identified as essential for differentiation. We selected the chromatin factor Ctbp2 from microarray data for its enriched expression in stem cells, in comparison to committed progenitors. RNA interference (RNAi) was used to knockdown gene expression in mouse ESCs and the potential for transduced cells to self-renew and differentiate was assessed in ESC and mesodermal assays. Here, we demonstrate an important role for Ctbp2 in stem cell maintenance and regulation of differentiation using an in vitro system. The knockdown of Ctbp2 increases the prevalence of ESCs in culture, delays differentiation induced by LIF withdrawal, and introduces developmental changes in mesodermal differentiation. A model is presented for the importance of Ctbp2 in maintaining a balance in decisions to self-renewal and differentiate.
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