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Stem Cell Reports. 2014 Nov 11;3(5):758-73. doi: 10.1016/j.stemcr.2014.08.015. Epub 2014 Oct 3.

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

Author information

1
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.
2
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.
3
Department of Molecular, Cell and Developmental Biology, UCLA, 621 Charles E. Young Drive East, Los Angeles, CA 90095, USA.
4
Eli and Edythe Broad Center for Regenerative Medicine, UCLA, Box 957357, Los Angeles, CA 90095, USA.
5
Microsoft Research, 1100 Glendon Avenue Suite PH1, Los Angeles, CA 90024, USA.
6
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. Electronic address: blowry@ucla.edu.

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.

PMID:
25316189
PMCID:
PMC4235151
DOI:
10.1016/j.stemcr.2014.08.015
[Indexed for MEDLINE]
Free PMC Article

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