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PMID: 20362537 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

MicroRNA-9 coordinates proliferation and migration of human embryonic stem cell-derived neural progenitors.

Cell stem cell ·Vol. 6 ·No. 4 ·2010-04-02 ·Pages 323-35

Delaloy C, Liu L, Lee JA, Su H, Shen F, Yang GY, Young WL, Ivey KN, Gao FB

Abstract

Human pluripotent stem cells offer promise for use in cell-based therapies for brain injury and diseases. However, their cellular behavior is poorly understood. Here we show that the expression of the brain-specific microRNA-9 (miR-9) is turned on in human neural progenitor cells (hNPCs) derived from human embryonic stem cells. Loss of miR-9 suppressed proliferation but promoted migration of hNPCs cultured in vitro. hNPCs without miR-9 activity also showed enhanced migration when transplanted into mouse embryonic brains or adult brains of a mouse model of stroke. These effects were not due to precocious differentiation of hNPCs. One of the key targets directly regulated by miR-9 encodes stathmin, which increases microtubule instability and whose expression in hNPCs correlates inversely with that of miR-9. Partial inhibition of stathmin activity suppressed the effects of miR-9 loss on proliferation and migration of human or embryonic rat neural progenitors. These results identify miR-9 as a novel regulator that coordinates the proliferation and migration of hNPCs.

MeSH Terms
Animals Cell Differentiation/genetics Cell Movement/genetics Cell Proliferation Embryonic Stem Cells/cytology,metabolism Gene Expression Regulation, Developmental Humans Mice MicroRNAs/genetics,metabolism Neurons/cytology,metabolism RNA, Messenger/genetics,metabolism Rats Stathmin/genetics,metabolism
Chemicals
MIRN92 microRNA, human MicroRNAs RNA, Messenger STMN1 protein, human Stathmin
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Delaloy Celine
Gladstone Institute of Neurological Disease and Department of Neurology, University of California-San Francisco, CA 94158, USA.
Liu Lei
Lee Jin-A
Su Hua
Shen Fanxia
Yang Guo-Yuan
Young William L
Ivey Kathy N
Gao Fen-Biao
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Article Info
Journal
Cell stem cell
Abbr.
Cell Stem Cell
ISSN
1875-9777
DOI
10.1016/j.stem.2010.02.015
Published
2010-04-02
Pages
323-35
Language
English
Region
United States
NLM ID
101311472
PMCID
PMC2851637
Subset
IM
Grants
NINDS NIH HHS · R01 NS066586 · United States
NINDS NIH HHS · R01 NS066586-06A2 · United States
NINDS NIH HHS · R01 NS066586-07 · United States
Corrections
CommentIn
PMID: 20362531
External Links
PubMed source DOI: 10.1016/j.stem.2010.02.015 PMC Full Text View journal details
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