Subventricular zone adult mouse neural stem cells require insulin receptor for self-renewal

Stem Cell Reports. 2022 Jun 14;17(6):1411-1427. doi: 10.1016/j.stemcr.2022.04.007. Epub 2022 May 5.

Abstract

The insulin receptor (INSR) is an evolutionarily conserved signaling protein that regulates development and cellular metabolism. INSR signaling promotes neurogenesis in Drosophila; however, a specific role for the INSR in maintaining adult neural stem cells (NSCs) in mammals has not been investigated. We show that conditionally deleting the Insr gene in adult mouse NSCs reduces subventricular zone NSCs by ∼70% accompanied by a corresponding increase in progenitors. Insr deletion also produced hyposmia caused by aberrant olfactory bulb neurogenesis. Interestingly, hippocampal neurogenesis and hippocampal-dependent behaviors were unperturbed. Highly aggressive proneural and mesenchymal glioblastomas had high INSR/insulin-like growth factor (IGF) pathway gene expression, and isolated glioma stem cells had an aberrantly high ratio of INSR:IGF type 1 receptor. Moreover, INSR knockdown inhibited GBM tumorsphere growth. Altogether, these data demonstrate that the INSR is essential for a subset of normal NSCs, as well as for brain tumor stem cell self-renewal.

Keywords: IGF-II; cancer stem cell; glioblastomas; insulin receptor; insulin-like growth factors; mouse; stem cell niche; subgranular zone; subventricular zone.

MeSH terms

  • Adult Stem Cells* / cytology
  • Adult Stem Cells* / metabolism
  • Animals
  • Lateral Ventricles / cytology
  • Lateral Ventricles / metabolism*
  • Mice
  • Neural Stem Cells* / cytology
  • Neural Stem Cells* / metabolism
  • Neurogenesis
  • Receptor, Insulin / metabolism*
  • Somatomedins* / metabolism

Substances

  • Somatomedins
  • Receptor, Insulin