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神经干细胞转录网络突出了神经系统发育所必需的基因。

Neural stem cell transcriptional networks highlight genes essential for nervous system development.

机构信息

The Gurdon Institute and The Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.

出版信息

EMBO J. 2009 Dec 16;28(24):3799-807. doi: 10.1038/emboj.2009.309.

Abstract

Neural stem cells must strike a balance between self-renewal and multipotency, and differentiation. Identification of the transcriptional networks regulating stem cell division is an essential step in understanding how this balance is achieved. We have shown that the homeodomain transcription factor, Prospero, acts to repress self-renewal and promote differentiation. Among its targets are three neural stem cell transcription factors, Asense, Deadpan and Snail, of which Asense and Deadpan are repressed by Prospero. Here, we identify the targets of these three factors throughout the genome. We find a large overlap in their target genes, and indeed with the targets of Prospero, with 245 genomic loci bound by all factors. Many of the genes have been implicated in vertebrate stem cell self-renewal, suggesting that this core set of genes is crucial in the switch between self-renewal and differentiation. We also show that multiply bound loci are enriched for genes previously linked to nervous system phenotypes, thereby providing a shortcut to identifying genes important for nervous system development.

摘要

神经干细胞必须在自我更新和多能性以及分化之间取得平衡。鉴定调节干细胞分裂的转录网络是理解如何实现这种平衡的重要步骤。我们已经表明,同源域转录因子 Prospero 起抑制自我更新和促进分化的作用。它的靶标之一是三种神经干细胞转录因子,Asense、Deadpan 和 Snail,其中 Asense 和 Deadpan 被 Prospero 抑制。在这里,我们在整个基因组中鉴定了这三个因子的靶标。我们发现它们的靶基因有很大的重叠,并且与 Prospero 的靶基因确实有很大的重叠,有 245 个基因组位点被所有因子结合。许多基因已被牵连到脊椎动物干细胞自我更新中,这表明这组核心基因在自我更新和分化之间的转换中至关重要。我们还表明,多结合位点富含先前与神经系统表型相关的基因,从而为鉴定对神经系统发育重要的基因提供了捷径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a14d/2797055/1b9f522acc18/emboj2009309f1.jpg

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