Cerebellar neural stem cells (NSCs) require Hedgehog-Gli (Hh-Gli) signalling for their maintenance and Nanog expression for their self-renewal. To identify novel molecular features of this regulatory pathway, we used next-generation sequencing technology to profile mRNA and microRNA expression in cerebellar NSCs, before and after induced differentiation (Diff-NSCs). Genes with higher transcript levels in NSCs (vs. Diff-NSCs) included Foxm1, which proved to be directly regulated by Gli and Nanog. Foxm1 in turn regulated several microRNAs that were overexpressed in NSCs: miR-130b, miR-301a, and members of the miR-15∼16 and miR-17∼92 clusters and whose knockdown significantly impaired the neurosphere formation ability. Our results reveal a novel Hh-Gli-Nanog-driven Foxm1-microRNA network that controls the self-renewal capacity of NSCs.
Besharat, Z. M., Abballe, L., Cicconardi, F., Bhutkar, A., Grassi, L., Le Pera, L., Moretti, M., Chinappi, M., D'Andrea, D., Mastronuzzi, A., Ianari, A., Vacca, A., De Smaele, E., Locatelli, F., Po, A., Miele, E., Ferretti, E., Foxm1 controls a pro-stemness microRNA network in neural stem cells, <<SCIENTIFIC REPORTS>>, 2018; 8 (1): 1-14. [doi:10.1038/s41598-018-21876-y] [https://hdl.handle.net/10807/229949]
Foxm1 controls a pro-stemness microRNA network in neural stem cells
Locatelli, FrancoWriting – Review & Editing
;
2018
Abstract
Cerebellar neural stem cells (NSCs) require Hedgehog-Gli (Hh-Gli) signalling for their maintenance and Nanog expression for their self-renewal. To identify novel molecular features of this regulatory pathway, we used next-generation sequencing technology to profile mRNA and microRNA expression in cerebellar NSCs, before and after induced differentiation (Diff-NSCs). Genes with higher transcript levels in NSCs (vs. Diff-NSCs) included Foxm1, which proved to be directly regulated by Gli and Nanog. Foxm1 in turn regulated several microRNAs that were overexpressed in NSCs: miR-130b, miR-301a, and members of the miR-15∼16 and miR-17∼92 clusters and whose knockdown significantly impaired the neurosphere formation ability. Our results reveal a novel Hh-Gli-Nanog-driven Foxm1-microRNA network that controls the self-renewal capacity of NSCs.
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
