title: MicroRNA-9 coordinates proliferation and migration of human embryonic stem cell-derived neural progenitors.
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.
authors.affiliation: Gladstone Institute of Neurological Disease and Department of Neurology, University of California, San Francisco, CA 94158, USA.
authors.forename: Celine
authors.initials: C
authors.lastname: Delaloy
authors.affiliation: Gladstone Institute of Neurological Disease and Department of Neurology, University of California, San Francisco, CA 94158, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Gladstone Institute of Neurological Disease and Department of Neurology, University of California, San Francisco, CA 94158, USA.
authors.forename: Jin-A
authors.initials: JA
authors.lastname: Lee
authors.affiliation: Center for Cerebrovascular Research, Departments of Anesthesia and Perioperative Care and Neurology and Neurosurgery, University of California, San Francisco, CA 94110, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Su
authors.affiliation: Center for Cerebrovascular Research, Departments of Anesthesia and Perioperative Care and Neurology and Neurosurgery, University of California, San Francisco, CA 94110, USA.
authors.forename: Fanxia
authors.initials: F
authors.lastname: Shen
authors.affiliation: Center for Cerebrovascular Research, Departments of Anesthesia and Perioperative Care and Neurology and Neurosurgery, University of California, San Francisco, CA 94110, USA.
authors.forename: Guo-Yuan
authors.initials: GY
authors.lastname: Yang
authors.affiliation: Center for Cerebrovascular Research, Departments of Anesthesia and Perioperative Care and Neurology and Neurosurgery, University of California, San Francisco, CA 94110, USA.
authors.forename: William L
authors.initials: WL
authors.lastname: Young
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA.
authors.forename: Kathy N
authors.initials: KN
authors.lastname: Ivey
authors.affiliation: 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.
authors.forename: Fen-Biao
authors.initials: FB
authors.lastname: Gao
mesh_terms: 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
chemical_list: C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C493995:STMN1 protein, human; D050777:Stathmin