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

Shravanthi Chidambaram, Fernando J. Velloso, Deborah E. Rothbard, Kaivalya Deshpande, Yvelande Cajuste, Kristin M. Snyder, Eduardo Fajardo, Andras Fiser, Nikos Tapinos, Steven W. Levison, Teresa L. Wood

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)1411-1427
Number of pages17
JournalStem Cell Reports
Issue number6
StatePublished - Jun 14 2022


  • IGF-II
  • cancer stem cell
  • glioblastomas
  • insulin receptor
  • insulin-like growth factors
  • mouse
  • stem cell niche
  • subgranular zone
  • subventricular zone

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology


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