MicroRNA-9 coordinates proliferation and migration of human embryonic stem cell-derived neural progenitors.
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.
Delaloy
Celine
C
Gladstone Institute of Neurological Disease and Department of Neurology, University of California, San Francisco, CA 94158, USA.
Liu
Lei
L
Gladstone Institute of Neurological Disease and Department of Neurology, University of California, San Francisco, CA 94158, USA.
Lee
Jin-A
JA
Gladstone Institute of Neurological Disease and Department of Neurology, University of California, San Francisco, CA 94158, USA.
Su
Hua
H
Center for Cerebrovascular Research, Departments of Anesthesia and Perioperative Care and Neurology and Neurosurgery, University of California, San Francisco, CA 94110, USA.
Shen
Fanxia
F
Center for Cerebrovascular Research, Departments of Anesthesia and Perioperative Care and Neurology and Neurosurgery, University of California, San Francisco, CA 94110, USA.
Yang
Guo-Yuan
GY
Center for Cerebrovascular Research, Departments of Anesthesia and Perioperative Care and Neurology and Neurosurgery, University of California, San Francisco, CA 94110, USA.
Young
William L
WL
Center for Cerebrovascular Research, Departments of Anesthesia and Perioperative Care and Neurology and Neurosurgery, University of California, San Francisco, CA 94110, USA.
Ivey
Kathy N
KN
Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA.
Gao
Fen-Biao
FB
Gladstone Institute of Neurological Disease and Department of Neurology, University of California, San Francisco, CA 94158, USA; Departments of Neurology and Neurobiology, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: fen-biao.gao@umassmed.edu.
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D050777:Stathmin / Q000235:genetics / Q000378:metabolism
C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C493995:STMN1 protein, human; D050777:Stathmin