Control of neural crest multipotency by Wnt signaling and the Lin28/let-7 axis
Control of neural crest multipotency by Wnt signaling and the Lin28/let-7 axis
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DOI：
10.7554/elife.40556
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发表时间：
2018-12-06
期刊：
影响因子：
7.7
通讯作者：
Simoes-Costa, Marcos
中科院分区：
文献类型：
--
作者：
Bhattacharya, Debadrita;Rothstein, Megan;Simoes-Costa, Marcos
细胞分化的一个关键步骤是多能性发育程序的沉默。虽然人们对谱系特异性基因如何被激活以产生不同的细胞类型了解甚多，但对抑制干性的机制却知之甚少。为了解决这个问题，我们研究了鸟类神经嵴细胞中维持祖细胞身份的转录网络的调节。我们的研究结果表明，由Wnt， Lin28a和let-7 mirna形成的调控回路以位置依赖的方式控制多能性程序的部署和随后的沉默。从多能性到分化的转变是由迁移细胞和背神经管之间的拓扑关系决定的，背神经管是产生wnt的干细胞生态位。我们的发现强调了一种快速沉默复杂调控程序的机制，并阐明了转录网络在细胞分化过程中如何响应位置信息。
A crucial step in cell differentiation is the silencing of developmental programs underlying multipotency. While much is known about how lineage-specific genes are activated to generate distinct cell types, the mechanisms driving suppression of stemness are far less understood. To address this, we examined the regulation of the transcriptional network that maintains progenitor identity in avian neural crest cells. Our results show that a regulatory circuit formed by Wnt, Lin28a and let-7 miRNAs controls the deployment and the subsequent silencing of the multipotency program in a position-dependent manner. Transition from multipotency to differentiation is determined by the topological relationship between the migratory cells and the dorsal neural tube, which acts as a Wnt-producing stem cell niche. Our findings highlight a mechanism that rapidly silences complex regulatory programs, and elucidate how transcriptional networks respond to positional information during cell differentiation.