Eli and Edythe Broad Center for Regenerative Medicine, UCLA, Box 957357, Los Angeles, CA 90095, USA; Department of Molecular, Cell and Developmental Biology, UCLA, 621 Charles E. Young Drive East, Los Angeles, CA 90095, USA.
Eli and Edythe Broad Center for Regenerative Medicine, UCLA, Box 957357, Los Angeles, CA 90095, USA; Department of Molecular, Cell and Developmental Biology, UCLA, 621 Charles E. Young Drive East, Los Angeles, CA 90095, USA; Molecular Biology Institute, UCLA, 611 Charles E. Young Drive East, Los Angeles, CA 90095, USA.
Stem Cell Reports. 2014 Nov 11;3(5):758-73. doi: 10.1016/j.stemcr.2014.08.015. Epub 2014 Oct 3.
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.
很明显，人类多能干细胞的神经分化产生了发育不成熟的细胞。在这里，我们表明 let-7 在人类神经祖细胞的发育决策中发挥功能作用，控制这些细胞是产生神经元还是神经胶质细胞。通过对组织和多能细胞的功能获得和功能丧失研究，我们的数据表明，let-7 通过调节关键染色质相关蛋白 HMGA2 特异性调节这一背景下的决策。此外，我们提供的证据表明，let-7/HMGA2 回路作用于 HES5，这是一个 NOTCH 效应物和成熟节点，调节神经系统中的命运决定。这些数据将 let-7 回路与 NOTCH 信号联系起来，并表明这种相互作用有助于调节人类的发育进程。
