Subventricular zone adult mouse neural stem cells require insulin receptor for self-renewal.
Subventricular zone adult mouse neural stem cells require insulin receptor for self-renewal.
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DOI：
10.1016/j.stemcr.2022.04.007
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发表时间：
2022-06-14
影响因子：
5.9
通讯作者：
Wood, Teresa L.
中科院分区：
文献类型：
--
作者：
Chidambaram, Shravanthi;Velloso, Fernando J.;Rothbard, Deborah E.;Deshpande, Kaivalya;Cajuste, Yvelande;Snyder, Kristin M.;Fajardo, Eduardo;Fiser, Andras;Tapinos, Nikos;Levison, Steven W.;Wood, Teresa L.
胰岛素受体（insulin receptor，INSR）是一种进化上保守的信号传导蛋白，调节发育和细胞代谢。INSR信号促进果蝇的神经发生;然而，在维持哺乳动物的成体神经干细胞（NSC）的INSR的具体作用尚未调查。我们表明，有条件地删除Insr基因在成年小鼠神经干细胞减少脑室下区神经干细胞的70%，伴随着相应的祖细胞的增加。Insr缺失也会引起异常嗅球神经发生引起的嗅觉减退。有趣的是，海马神经发生和海马依赖性行为未受干扰。高度侵袭性的前神经和间充质胶质母细胞瘤具有高INSR/胰岛素样生长因子（IGF）途径基因表达，并且分离的胶质瘤干细胞具有异常高的INSR：IGF 1型受体比率。此外，INSR敲低抑制GBM肿瘤球生长。总之，这些数据表明，INSR是一个子集的正常神经干细胞，以及脑肿瘤干细胞自我更新所必需的。胰岛素受体（INSR）是成年SVZ神经干细胞自我更新所必需的INSR缺失导致嗅觉减退伴嗅球神经发生增加海马干细胞（及相关行为）不需要INSR胶质母细胞瘤过表达肿瘤球生长所需的INSR途径组分Levison，Wood，and colleagues（奇丹巴拉姆et al.）显示有条件地缺失成年鼠神经干细胞（NSC）中的胰岛素受体（INSR）会耗尽室下区中的NSC并相应地增加祖细胞，导致异常嗅球神经发生引起的嗅觉减退。相反，海马神经发生是不受干扰的。他们还表明，INSR是人类胶质母细胞瘤肿瘤球自我更新所必需的。
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. Insulin receptor (INSR) is essential for adult SVZ neural stem cell self-renewal INSR deletion causes hyposmia with increased olfactory bulb neurogenesis Hippocampal stem cells (and associated behaviors) do not require INSR Glioblastomas overexpress INSR pathway components required for tumorsphere growth Levison, Wood, and colleagues (Chidambaram et al.) show that conditionally deleting the insulin receptor (INSR) in adult murine neural stem cells (NSCs) depletes NSCs in the subventricular zone and correspondingly increases progenitors, resulting in hyposmia caused by aberrant olfactory bulb neurogenesis. In contrast, hippocampal neurogenesis is unperturbed. They also show that the INSR is necessary for human glioblastoma tumorsphere self-renewal.
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影响因子：
2.9
作者：
Buono KD;Vadlamuri D;Gan Q;Levison SW
通讯作者：
Levison SW
影响因子：
16.2
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Lehtinen MK;Zappaterra MW;Chen X;Yang YJ;Hill AD;Lun M;Maynard T;Gonzalez D;Kim S;Ye P;D'Ercole AJ;Wong ET;LaMantia AS;Walsh CA
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64.5
作者：
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通讯作者：
EFSTRATIADIS, A
影响因子：
4
作者：
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通讯作者：
Lund, P. Kay
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作者：
Raitano S;Verfaillie CM;Petryk A
通讯作者：
Petryk A