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.
Foxm1 controls a pro-stemness microRNA network in neural stem cells / Besharat, Zein Mersini; Abballe, Luana; Cicconardi, Francesco; Bhutkar, Arjun; Grassi, Luigi; Le Pera, Loredana; Moretti, Marta; Chinappi, Mauro; D'Andrea, Daniel; Mastronuzzi, Angela; Ianari, Alessandra; Vacca, Alessandra; De Smaele, Enrico; Locatelli, Franco; Po, Agnese; Miele, Evelina; Ferretti, Elisabetta. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - ELETTRONICO. - 8:1(2018), p. 3523. [10.1038/s41598-018-21876-y]
Foxm1 controls a pro-stemness microRNA network in neural stem cells
Besharat, Zein Mersini;Abballe, Luana;Cicconardi, Francesco;GRASSI, LUIGIMethodology
;Le Pera, Loredana;Moretti, MartaMethodology
;Chinappi, Mauro;D'Andrea, Daniel;Mastronuzzi, Angela;Ianari, Alessandra;Vacca, Alessandra;De Smaele, Enrico;Locatelli, Franco;Po, Agnese
;Miele, Evelina;Ferretti, Elisabetta
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.| File | Dimensione | Formato | |
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Besharat_Foxm1_2018.pdf
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