Early stem cell aging in the mature brain.
Early stem cell aging in the mature brain.
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DOI：
10.1016/j.stem.2021.03.018
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发表时间：
2021-05-06
期刊：
影响因子：
23.9
通讯作者：
Bonaguidi MA
中科院分区：
文献类型：
--
作者：
Ibrayeva A;Bay M;Pu E;Jörg DJ;Peng L;Jun H;Zhang N;Aaron D;Lin C;Resler G;Hidalgo A;Jang MH;Simons BD;Bonaguidi MA
干细胞功能障碍导致许多与年龄相关的疾病。识别最初损害干细胞行为的机制代表了促进生命后期组织功能的早期目标。在这里，我们指出了多种因素，破坏神经干细胞（NSC）在成年海马体的行为。克隆追踪显示，通过鉴定短期（ST-NSC）和长期（LT-NSC），NSC表现出异步消耗。ST-NSC迅速分裂产生神经元，并在年轻的大脑中耗尽。与此同时，多能LT-NSC维持数月，但通过延长静止期而被推出稳态。对深层NSC静止期的单细胞转录组分析揭示了成熟大脑中分子衰老的几个标志，并确定酪氨酸蛋白激酶BK 1是NSC促衰老因子。在中年人大脑中，用α-抑制剂伊马替尼治疗增加了NSC的激活，而不损害NSC的维持。我们的研究表明，海马神经干细胞是特别脆弱和适应细胞老化。Eschyeva等人证明，长期神经干细胞（NSC）通过加深静止而失去稳态，并在成熟大脑中表现出分子老化。他们还确定了NSC 1作为NSC促衰老因子，并表明NSC抑制剂伊马替尼可以在以后的生活中部分恢复NSC功能。
Stem cell dysfunction drives many age-related disorders. Identifying mechanisms that initially compromise stem cell behavior represent early targets to promote tissue function later in life. Here, we pinpoint multiple factors that disrupt neural stem cell (NSC) behavior in the adult hippocampus. Clonal tracing showed that NSCs exhibit asynchronous depletion by identifying short-term (ST-NSC) and long-term NSCs (LT-NSCs). ST-NSC divide rapidly to generate neurons and deplete in the young brain. Meanwhile, multipotent LT-NSCs are maintained for months, but are pushed out of homeostasis by lengthening quiescence. Single cell transcriptome analysis of deep NSC quiescence revealed several hallmarks of molecular aging in the mature brain and identified tyrosine-protein kinase Abl1 as an NSC pro-aging factor. Treatment with the Abl-inhibitor Imatinib increased NSC activation without impairing NSC maintenance in the middle-aged brain. Our study indicates that hippocampal NSCs are particularly vulnerable and adaptable to cellular aging. Ibrayeva et al. demonstrate that long-term neural stem cells (NSCs) lose homeostasis through deepening quiescence and exhibit molecular aging in the mature brain. They also identify Abl1 as a NSC pro-aging factor and show that the Abl-inhibitor Imatinib can partially restore NSC function later in life.
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影响因子：
--
作者：
Berg DA;Bond AM;Ming GL;Song H
通讯作者：
Song H
影响因子：
64.5
作者：
Bonaguidi MA;Wheeler MA;Shapiro JS;Stadel RP;Sun GJ;Ming GL;Song H
通讯作者：
Song H
影响因子：
64.5
作者：
de Cabo R;Carmona-Gutierrez D;Bernier M;Hall MN;Madeo F
通讯作者：
Madeo F
DOI：
10.1073/pnas.0601992103
发表时间：
2006-05-23
影响因子：
11.1
作者：
Encinas, Juan M.;Vaahtokari, Anne;Enikolopov, Grigori
通讯作者：
Enikolopov, Grigori
影响因子：
7.2
作者：
Bonaguidi, Michael A.;Stadel, Ryan P.;Song, Hongjun
通讯作者：
Song, Hongjun