Foxm1 controls a pro-stemness microRNA network in neural stem cells

Sci Rep. 2018 Feb 23;8(1):3523. doi: 10.1038/s41598-018-21876-y.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Differentiation
  • Cell Proliferation
  • Cerebellum / cytology
  • Cerebellum / growth & development
  • Cerebellum / metabolism*
  • Forkhead Box Protein M1 / genetics*
  • Forkhead Box Protein M1 / metabolism
  • Gene Expression Regulation, Developmental*
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism
  • High-Throughput Nucleotide Sequencing
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Nanog Homeobox Protein / genetics*
  • Nanog Homeobox Protein / metabolism
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*
  • Neurogenesis / genetics*
  • Primary Cell Culture
  • Signal Transduction
  • Spheroids, Cellular / cytology
  • Spheroids, Cellular / metabolism
  • Zinc Finger Protein GLI1 / genetics*
  • Zinc Finger Protein GLI1 / metabolism


  • Forkhead Box Protein M1
  • Foxm1 protein, mouse
  • Gli1 protein, mouse
  • Hedgehog Proteins
  • MIRN130 microRNA, mouse
  • MIRN17-92 microRNA, mouse
  • MIRN301 microRNA, mouse
  • MicroRNAs
  • Mirn15a microRNA, mouse
  • Nanog Homeobox Protein
  • Nanog protein, mouse
  • Shh protein, mouse
  • Zinc Finger Protein GLI1