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.
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.
Chunnian
C
Zhao
GuoQiang
G
Sun
Shengxiu
S
Li
Ming-Fei
MF
Lang
Su
S
Yang
Wendong
W
Li
Yanhong
Y
Shi
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