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

doi:10.1016/j.stemcr.2022.04.007

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

Systems & Computational Biology

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1411-1427
Number of pages	17
Journal	Stem Cell Reports
Volume	17
Issue number	6
DOIs	https://doi.org/10.1016/j.stemcr.2022.04.007
State	Published - Jun 14 2022

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.stemcr.2022.04.007

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title = "Subventricular zone adult mouse neural stem cells require insulin receptor for self-renewal",

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",

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

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doi = "10.1016/j.stemcr.2022.04.007",

language = "English (US)",

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AU - Chidambaram, Shravanthi

AU - Velloso, Fernando J.

AU - Rothbard, Deborah E.

AU - Deshpande, Kaivalya

AU - Cajuste, Yvelande

AU - Snyder, Kristin M.

AU - Fajardo, Eduardo

AU - Fiser, Andras

AU - Tapinos, Nikos

AU - Levison, Steven W.

AU - Wood, Teresa L.

PY - 2022/6/14

Y1 - 2022/6/14

N2 - 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.

AB - 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.

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KW - subgranular zone

KW - subventricular zone

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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