Coordinated changes in cellular behavior ensure the lifelong maintenance of the hippocampal stem cell population.
Coordinated changes in cellular behavior ensure the lifelong maintenance of the hippocampal stem cell population.
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细胞行为的协调变化确保了海马干细胞种群的终身维持。
DOI：
10.1016/j.stem.2021.01.003
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发表时间：
2021-05-06
期刊：
影响因子：
23.9
通讯作者：
Guillemot F
中科院分区：
文献类型：
--
作者：
Harris L;Rigo P;Stiehl T;Gaber ZB;Austin SHL;Masdeu MDM;Edwards A;Urbán N;Marciniak-Czochra A;Guillemot F
神经干细胞数量在幼年小鼠的海马体中迅速下降，但在成年期稳定，确保终身海马体神经发生。我们表明，年轻人干细胞数量的稳定是干细胞行为协调变化的结果。虽然在青少年中增殖的神经干细胞分化迅速，但它们越来越多地返回到浅静止的静止状态，并在成年后通过额外的自我更新分裂进行进展。单细胞转录组学，建模和标签保留分析表明，休眠细胞具有更高的激活率和更大的贡献比休眠细胞，没有离开静止神经发生。干细胞行为的这些变化是由于翻译后降解增加而导致的前活化蛋白ASCL1表达的逐渐减少。这些细胞机制有助于调和目前海马神经干细胞（NSC）动力学的矛盾模型，并可能有助于在哺乳动物物种，包括人类的海马神经发生的不同速度下降。随着年龄的增长，更多增殖的海马干细胞恢复到浅静止状态，随着年龄的增长，海马干细胞进入更深的静止状态。这些变化推动了从发育到成年神经发生的转变。表明在小鼠的早期生命中，多种细胞变化协同作用，以在整个成年期保持海马干细胞群。特别是，更多的增殖干细胞恢复到静止状态，而不是分化。这些变化通过增加促活化因子ASCL1的降解来协调。
Neural stem cell numbers fall rapidly in the hippocampus of juvenile mice but stabilize during adulthood, ensuring lifelong hippocampal neurogenesis. We show that this stabilization of stem cell numbers in young adults is the result of coordinated changes in stem cell behavior. Although proliferating neural stem cells in juveniles differentiate rapidly, they increasingly return to a resting state of shallow quiescence and progress through additional self-renewing divisions in adulthood. Single-cell transcriptomics, modeling, and label retention analyses indicate that resting cells have a higher activation rate and greater contribution to neurogenesis than dormant cells, which have not left quiescence. These changes in stem cell behavior result from a progressive reduction in expression of the pro-activation protein ASCL1 because of increased post-translational degradation. These cellular mechanisms help reconcile current contradictory models of hippocampal neural stem cell (NSC) dynamics and may contribute to the different rates of decline of hippocampal neurogenesis in mammalian species, including humans. More proliferating hippocampal stem cells return to shallow quiescence with age Dormant stem cells enter deeper quiescence with age These changes drive the transition from developmental to adult neurogenesis Increasing degradation of ASCL1 protein by HUWE1 coordinates these changes Harris et al. show that multiple cellular changes work in concert during early life to preserve the hippocampal stem cell population throughout adulthood in mice. In particular, more proliferating stem cells return to quiescence instead of differentiating. The changes are coordinated by increasing degradation of the pro-activation factor ASCL1.
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影响因子：
46.9
作者：
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DOI：
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通讯作者：
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