reversible block of mouse neural stem cell differentiation in the absence of dicer and micrornas可逆的小鼠神经干细胞分化没有帽子和小分子核糖核酸.pdfVIP

Reversible Block of Mouse Neural Stem Cell Differentiation in the Absence of Dicer and MicroRNAs 1,2. 1,2. 1,2 ¨ 1,2 Therese Andersson , Sabhi Rahman , Stephen N. Sansom , Jessica M. Alsio , Masahiro 1¤a 1,2 3¤b 3 1,2 Kaneda , James Smith , Donal O’Carroll , Alexander Tarakhovsky , Frederick J. Livesey * 1 Gurdon Institute, University of Cambridge, Cambridge, United Kingdom, 2 Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom, 3 Laboratory of Lymphocyte Signalling, The Rockefeller University, New York, United States of America Abstract Background: To investigate the functions of Dicer and microRNAs in neural stem (NS) cell self-renewal and neurogenesis, we established neural stem cell lines from the embryonic mouse Dicer-null cerebral cortex, producing neural stem cell lines that lacked all microRNAs. Principal Findings: Dicer-null NS cells underwent normal self-renewal and could be maintained in vitro indefinitely, but had subtly altered cell cycle kinetics and abnormal heterochromatin organisation. In the absence of all microRNAs, Dicer-null NS cells were incapable of generating either glial or neuronal progeny and exhibited a marked dependency on exogenous EGF for survival. Dicer-null NS cells assumed complex differences in mRNA and protein expression under self-renewing conditions, upregulating transcripts indicative of self-renewing NS cells and expressing genes characteristic of differentiating neurons