Peer-Reviewed Journal Details
Mandatory Fields
Topol A;Zhu S;Hartley BJ;English J;Hauberg ME;Tran N;Rittenhouse CA;Simone A;Ruderfer DM;Johnson J;Readhead B;Hadas Y;Gochman PA;Wang YC;Shah H;Cagney G;Rapoport J;Gage FH;Dudley JT;Sklar P;Mattheisen M;Cotter D;Fang G;Brennand KJ;
2016
May
Cell Reports
Dysregulation of miRNA-9 in a Subset of Schizophrenia Patient-Derived Neural Progenitor Cells.
Validated
Optional Fields
15
5
Converging evidence indicates that microRNAs (miRNAs) may contribute to disease risk for schizophrenia (SZ). We show that microRNA-9 (miR-9) is abundantly expressed in control neural progenitor cells (NPCs) but also significantly downregulated in a subset of SZ NPCs. We observed a strong correlation between miR-9 expression and miR-9 regulatory activity in NPCs as well as between miR-9 levels/activity, neural migration, and diagnosis. Overexpression of miR-9 was sufficient to ameliorate a previously reported neural migration deficit in SZ NPCs, whereas knockdown partially phenocopied aberrant migration in control NPCs. Unexpectedly, proteomic- and RNA sequencing (RNA-seq)-based analysis revealed that these effects were mediated primarily by small changes in expression of indirect miR-9 targets rather than large changes in direct miR-9 targets; these indirect targets are enriched for migration-associated genes. Together, these data indicate that aberrant levels and activity of miR-9 may be one of the many factors that contribute to SZ risk, at least in a subset of patients.
2211-1247
10.1016/j.celrep.2016.03.090
Grant Details