小柯机器人

美国南加州大学Michael A. Bonaguidi小组的最新研究揭示了成人大脑中早期干细胞衰老的机制。相关论文于2021年4月12日在线发表在《细胞-干细胞》杂志上。

研究人员揭示了破坏成人海马中神经干细胞（NSC）功能的多种因素。克隆跟踪表明，NSC通过识别短期NSC（ST-NSC）和长期NSC（LT-NSC）而表现出异步耗竭。ST-NSC迅速分裂产生神经元，并在年轻大脑中耗竭。同时，多能性LT-NSC可以存在数月之久，但由于延长的静止期而无法达到稳态。

深层静止NSC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，并发现酪氨酸蛋白激酶Abl1是NSC的衰老因子。用Abl抑制剂伊马替尼治疗可增强NSC活化，同时也不会损害中年人脑中NSC的维持。该研究表明，海马神经干细胞虽然特别脆弱，但也能够适应细胞衰老 。

据悉，干细胞功能紊乱会产生许多与年龄有关的疾病。揭示干细胞早期行为的识别机制对发现生命后期促进组织功能的靶标至关重要。

附：英文原文

Title: Early stem cell aging in the mature brain

Author: Albina Ibrayeva, Maxwell Bay, Elbert Pu, David J. Jrg, Lei Peng, Heechul Jun, Naibo Zhang, Daniel Aaron, Congrui Lin, Galen Resler, Axel Hidalgo, Mi-Hyeon Jang, Benjamin D. Simons, Michael A. Bonaguidi

Issue&Volume: 2021-04-12

Abstract: Stem cell dysfunction drives many age-related disorders. Identifying mechanisms thatinitially compromise stem cell behavior represent early targets to promote tissuefunction later in life. Here, we pinpoint multiple factors that disrupt neural stemcell (NSC) behavior in the adult hippocampus. Clonal tracing showed that NSCs exhibitasynchronous depletion by identifying short-term NSCs (ST-NSCs) and long-term NSCs(LT-NSCs). ST-NSCs divide rapidly to generate neurons and deplete in the young brain.Meanwhile, multipotent LT-NSCs are maintained for months but are pushed out of homeostasisby lengthening quiescence. Single-cell transcriptome analysis of deep NSC quiescencerevealed several hallmarks of molecular aging in the mature brain and identified tyrosine-proteinkinase Abl1 as an NSC aging factor. Treatment with the Abl inhibitor imatinib increasedNSC activation without impairing NSC maintenance in the middle-aged brain. Our studyindicates that hippocampal NSCs are particularly vulnerable and adaptable to cellularaging.

DOI: 10.1016/j.stem.2021.03.018

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00124-7

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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