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Let-7 miRNAs can act through notch to regulate human gliogenesis.

ABSTRACT: 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.

SUBMITTER: Patterson M

PROVIDER: S-EPMC4235151 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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let-7 miRNAs can act through notch to regulate human gliogenesis.

Patterson M M Gaeta X X Loo K K Edwards M M Smale S S Cinkornpumin J J Xie Y Y Listgarten J J Azghadi S S Douglass S M SM Pellegrini M M Lowry W E WE

Stem cell reports 20141003 5

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- ...[more]

PMID: 25316189

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