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剖析原始态和启动态多能性状态之间转录调控回路的差异。

Dissecting the variation in transcriptional circuits between naive and primed pluripotent states.

作者信息

Deb Aritra, Sarkar Arijita, Ghosh Zhumur

机构信息

Bioinformatics Centre, Bose Institute, Kolkata, India.

出版信息

FEBS Lett. 2017 Aug;591(15):2362-2375. doi: 10.1002/1873-3468.12732. Epub 2017 Jul 14.

Abstract

Naive and primed pluripotent states are very similar to each other, but subtle differences exist in their maintenance and differentiation programmes. Transcription factors (TFs) play a key role towards maintaining pluripotency and cellular reprogramming. However, TF expression dynamics and regulatory mechanisms in naive and primed pluripotent states are poorly understood. Here, we performed a comprehensive transcriptional analysis of both states, which revealed a gene expression pattern in mESCs (naive state) that appear to be distinct from mEpiSCs (primed state). We screened 10 TFs essential for maintenance, self-renewal and differentiation, of which the TFs- Notch3, Meis1, Gli3 and Srf can act as novel markers distinguishing the two states. Furthermore, a detailed bioinformatic analysis (involving these TFs) elucidated essential transcriptional circuits between the naive and primed pluripotent states.

摘要

幼稚多能状态和引发多能状态彼此非常相似,但在其维持和分化程序中存在细微差异。转录因子(TFs)在维持多能性和细胞重编程方面起着关键作用。然而,对于幼稚多能状态和引发多能状态下的转录因子表达动态和调控机制,我们了解甚少。在这里,我们对这两种状态进行了全面的转录分析,结果揭示了小鼠胚胎干细胞(幼稚状态)中的一种基因表达模式,该模式似乎与小鼠胚外内胚层干细胞(引发状态)不同。我们筛选了维持、自我更新和分化所必需的10种转录因子,其中转录因子Notch3、Meis1、Gli3和Srf可作为区分这两种状态的新标志物。此外,一项详细的生物信息学分析(涉及这些转录因子)阐明了幼稚多能状态和引发多能状态之间的关键转录回路。

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