TY - JOUR
T1 - MicroRNA-153 Regulates the Acquisition of Gliogenic Competence by Neural Stem Cells
AU - Tsuyama, Jun
AU - Bunt, Jens
AU - Richards, Linda J.
AU - Iwanari, Hiroko
AU - Mochizuki, Yasuhiro
AU - Hamakubo, Takao
AU - Shimazaki, Takuya
AU - Okano, Hideyuki
N1 - Funding Information:
We thank Dr. H. Miyoshi (RIKEN BioResource Center, Keio University) for the lentivirus constructs, Dr. H. Niwa for providing the EBRTcH3 ESCs and the pCAGGS-LIF vector, Dr. H. Naka-Kaneda (RIKEN Center for Integrative Medical Sciences) for providing the miRNA array data, Dr. H. Kanki (Saga-Ken Medical Centre Koseikan) for providing the lentivirus vector CSII-EF-RfA-Kor, Drs. K. Ishii and K. Nakajima (Keio University) for assistance with the IUE experiments, and all members of the H.O. laboratory for encouragement and support. This study was supported by a Grant-in-Aid for Scientific Research on Innovative Areas entitled “Neural Diversity and Neocortical Organization” from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan (to T.S.); National Health and Medical Research Council (NHMRC, Australia) grant 1048849; Australian Research Council grant DP140101499 (to L.J.R); Grants-in-Aid for Scientific Research from MEXT (to T.S. and H.O.), and by a Grant-in-Aid from the Japan Society for the Promotion of Science Research Fellowship Program (to J.T.). L.J.R. is supported by an NHMRC Principal Research Fellowship. H.O. is a paid scientific advisory board consultant for San Bio.
Publisher Copyright:
© 2015 The Authors.
PY - 2015/9/8
Y1 - 2015/9/8
N2 - Summary Mammalian neural stem/progenitor cells (NSPCs) sequentially generate neurons and glia during CNS development. Here we identified miRNA-153 (miR-153) as a modulator of the temporal regulation of NSPC differentiation. Overexpression (OE) of miR-153 delayed the onset of astrogliogenesis and maintained NSPCs in an undifferentiated state in vitro and in the developing cortex. The transcription factors nuclear factor I (NFI) A and B, essential regulators of the initiation of gliogenesis, were found to be targets of miR-153. Inhibition of miR-153 in early neurogenic NSPCs induced precocious gliogenesis, whereas NFIA/B overexpression rescued the anti-gliogenic phenotypes induced by miR-153 OE. Our results indicate that miR-mediated fine control of NFIA/B expression is important in the molecular networks that regulate the acquisition of gliogenic competence by NSPCs in the developing CNS.Gliogenesis is tightly inhibited during the early neurogenic phase of central nervous system development. Okano, Shimazaki, and colleagues identified a microRNA, miR-153, as an inhibitor of gliogenesis in early neurogenic neural stem/progenitor cells (NSPCs). This study demonstrates that miR-153 controls the timing of the acquisition of gliogenic competence via direct repression of the gliogenic transcription factors NFIA and NFIB.
AB - Summary Mammalian neural stem/progenitor cells (NSPCs) sequentially generate neurons and glia during CNS development. Here we identified miRNA-153 (miR-153) as a modulator of the temporal regulation of NSPC differentiation. Overexpression (OE) of miR-153 delayed the onset of astrogliogenesis and maintained NSPCs in an undifferentiated state in vitro and in the developing cortex. The transcription factors nuclear factor I (NFI) A and B, essential regulators of the initiation of gliogenesis, were found to be targets of miR-153. Inhibition of miR-153 in early neurogenic NSPCs induced precocious gliogenesis, whereas NFIA/B overexpression rescued the anti-gliogenic phenotypes induced by miR-153 OE. Our results indicate that miR-mediated fine control of NFIA/B expression is important in the molecular networks that regulate the acquisition of gliogenic competence by NSPCs in the developing CNS.Gliogenesis is tightly inhibited during the early neurogenic phase of central nervous system development. Okano, Shimazaki, and colleagues identified a microRNA, miR-153, as an inhibitor of gliogenesis in early neurogenic neural stem/progenitor cells (NSPCs). This study demonstrates that miR-153 controls the timing of the acquisition of gliogenic competence via direct repression of the gliogenic transcription factors NFIA and NFIB.
UR - http://www.scopus.com/inward/record.url?scp=84941170340&partnerID=8YFLogxK
U2 - 10.1016/j.stemcr.2015.06.006
DO - 10.1016/j.stemcr.2015.06.006
M3 - Article
C2 - 26212661
AN - SCOPUS:84941170340
SN - 2213-6711
VL - 5
SP - 365
EP - 377
JO - Stem Cell Reports
JF - Stem Cell Reports
IS - 3
ER -