let-7 miRNAs can act through notch to regulate human gliogenesis.
let-7 miRNAs can act through notch to regulate human gliogenesis.
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DOI：
10.1016/j.stemcr.2014.08.015
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发表时间：
2014-11-11
影响因子：
5.9
通讯作者：
Lowry, W. E.
中科院分区：
文献类型：
--
作者：
Patterson, M.;Gaeta, X.;Loo, K.;Edwards, M.;Smale, S.;Cinkornpumin, J.;Xie, Y.;Listgarten, J.;Azghadi, S.;Douglass, S. M.;Pellegrini, M.;Lowry, W. E.
显然，从人类多能干细胞分化而来的神经会产生发育不成熟的细胞。在这里，我们展示了let-7在人类神经前体细胞的发育决策中发挥的功能作用，控制这些细胞是生成神经元还是胶质细胞。通过对组织和多能来源细胞的功能获得和功能丧失的研究，我们的数据表明，let-7通过调节关键的染色质相关蛋白HMGA2来特异性地调节这方面的决策。此外，我们提供了LET-7/HMGA2电路作用于HES5的证据，HES5是一个缺口效应器和成熟的节点，调节神经系统中的命运决定。这些数据将let-7电路连接到缺口信号，并表明这种相互作用有助于调节人类的发育进程。Let-7 miRNAs影响神经前体细胞的发育成熟度，let-7 miRNAs通过HMGA2和Notch发挥作用，调节神经胶质细胞的形成。HMGA2的表达调节NICD对HES5启动子的访问。他们确定LET-7靶基因HMGA2和Notch效应器HES5是调节从神经发生到胶质发生转变的途径中的关键节点，并展示了HMGA2允许访问HES5启动子的调节机制。
It is clear that neural differentiation from human pluripotent stem cells generates cells that are developmentally immature. Here, we show that the let-7 plays a functional role in the developmental decision making of human neural progenitors, controlling whether these cells make neurons or glia. Through gain- and loss-of-function studies on both tissue and pluripotent derived cells, our data show that let-7 specifically regulates decision making in this context by regulation of a key chromatin-associated protein, HMGA2. Furthermore, we provide evidence that the let-7/HMGA2 circuit acts on HES5, a NOTCH effector and well-established node that regulates fate decisions in the nervous system. These data link the let-7 circuit to NOTCH signaling and suggest that this interaction serves to regulate human developmental progression. let-7 miRNAs influence developmental maturity of neural progenitors let-7 miRNAs act through HMGA2 and NOTCH to regulate gliogenesis HMGA2 expression regulates access of NICD to HES5 promoter Induction of let-7 miRNAs can accelerate oligodendrogenesis Lowry and colleagues investigate the role of let-7 miRNAs in human neural progenitor cell developmental maturation and fate decisions. They identify HMGA2, a let-7 target gene, and HES5, a Notch effector, as critical nodes in a pathway regulating a transition from neurogenesis to gliogenesis, and demonstrate a regulatory mechanism by which HMGA2 allows access to the HES5 promoter.
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影响因子：
4.1
作者：
Graf R;Munschauer M;Mastrobuoni G;Mayr F;Heinemann U;Kempa S;Rajewsky N;Landthaler M
通讯作者：
Landthaler M
影响因子：
64.5
作者：
Bhatt DM;Pandya-Jones A;Tong AJ;Barozzi I;Lissner MM;Natoli G;Black DL;Smale ST
通讯作者：
Smale ST
DOI：
10.1073/pnas.1220176110
发表时间：
2013-08-06
影响因子：
11.1
作者：
Cimadamore, Flavio;Amador-Arjona, Alejandro;Terskikh, Alexey V.
通讯作者：
Terskikh, Alexey V.
影响因子：
5.3
作者：
Craig, A;Luo, NL;Back, SA
通讯作者：
Back, SA
影响因子：
2.9
作者：
Hirabayashi, Y;Gotoh, Y
通讯作者：
Gotoh, Y