MicroRNA let-7b regulates neural stem cell proliferation and differentiation by targeting nuclear receptor TLX signaling.
Neural stem cell self-renewal and differentiation is orchestrated by precise control of gene expression involving nuclear receptor TLX. Let-7b, a member of the let-7 microRNA family, is expressed in mammalian brains and exhibits increased expression during neural differentiation. However, the role of let-7b in neural stem cell proliferation and differentiation remains unknown. Here we show that let-7b regulates neural stem cell proliferation and differentiation by targeting the stem cell regulator TLX and the cell cycle regulator cyclin D1. Overexpression of let-7b led to reduced neural stem cell proliferation and increased neural differentiation, whereas antisense knockdown of let-7b resulted in enhanced proliferation of neural stem cells. Moreover, in utero electroporation of let-7b to embryonic mouse brains led to reduced cell cycle progression in neural stem cells. Introducing an expression vector of Tlx or cyclin D1 that lacks the let-7b recognition site rescued let-7b-induced proliferation deficiency, suggesting that both TLX and cyclin D1 are important targets for let-7b-mediated regulation of neural stem cell proliferation. Let-7b, by targeting TLX and cyclin D1, establishes an efficient strategy to control neural stem cell proliferation and differentiation.
Zhao
Chunnian
C
Department of Neurosciences, Center for Gene Expression and Drug Discovery, Beckman Research Institute of City of Hope, 1500 E Duarte Rd, Duarte, CA 91010, USA.
Sun
GuoQiang
G
Li
Shengxiu
S
Lang
Ming-Fei
MF
Yang
Su
S
Li
Wendong
W
Shi
Yanhong
Y
D020413:3' Untranslated Regions; D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D018274:Electroporation; D005260:Female; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D011247:Pregnancy; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D020413:3' Untranslated Regions; C530105:Ccnd1 protein, mouse; D035683:MicroRNAs; C490258:Nr2e1 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; C542687:mirnlet7 microRNA, mouse; D019938:Cyclin D1