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通过 Myc/Max 转录复合物非依赖性机制实现 ESC 的无限自我更新。

Indefinite self-renewal of ESCs through Myc/Max transcriptional complex-independent mechanisms.

机构信息

Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical University, Yamane Hidaka, Saitama, Japan.

出版信息

Cell Stem Cell. 2011 Jul 8;9(1):37-49. doi: 10.1016/j.stem.2011.04.020.

DOI:10.1016/j.stem.2011.04.020
PMID:21726832
Abstract

Embryonic stem cells (ESCs) can self-renew indefinitely under the governance of ESC-specific transcriptional circuitries in which each transcriptional factor regulates distinct or overlapping sets of genes with other factors. c-Myc is a key player that is crucially involved in maintaining the undifferentiated state and the self-renewal of ESCs. However, the mechanism by which c-Myc helps preserve the ESC status is still poorly understood. Here we addressed this question by performing loss-of-function studies with the Max gene, which encodes the best-characterized partner protein for all Myc family proteins. Although Myc/Max complexes are widely regarded as crucial regulators of the ESC status, our data revealed that ESCs do not absolutely require these complexes in certain contexts and that this requirement is restricted to empirical ESC culture conditions without a MAPK inhibitor.

摘要

胚胎干细胞(ESCs)在 ESC 特异性转录调控回路的控制下可以无限自我更新,其中每个转录因子与其他因子一起调节不同或重叠的基因集。c-Myc 是一个关键因子,它在维持未分化状态和 ESCs 的自我更新中起着至关重要的作用。然而,c-Myc 帮助维持 ESC 状态的机制仍知之甚少。在这里,我们通过使用 Max 基因进行功能丧失研究来解决这个问题,Max 基因编码所有 Myc 家族蛋白的最佳特征性伴侣蛋白。尽管 Myc/Max 复合物被广泛认为是 ESC 状态的关键调节因子,但我们的数据表明,在某些情况下,ESCs 并非绝对需要这些复合物,并且这种需求仅限于没有 MAPK 抑制剂的经验性 ESC 培养条件。

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