Age-related neurogenesis decline in the subventricular zone is associated with specific cell cycle regulation changes in activated neural stem cells.
Age-related neurogenesis decline in the subventricular zone is associated with specific cell cycle regulation changes in activated neural stem cells.
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DOI：
10.1038/srep21505
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发表时间：
2016-02-19
影响因子：
4.6
通讯作者：
Boussin FD
中科院分区：
文献类型：
--
作者：
Daynac M;Morizur L;Chicheportiche A;Mouthon MA;Boussin FD
尽管神经干细胞（NSCs）在哺乳动物的整个成年期都能维持持续的神经发生，但它们逐渐表现出增殖缺陷，这有助于在衰老过程中心室下神经发生的急剧减少。然而，关于神经源性生态位的早期年龄相关事件知之甚少。使用荧光激活细胞分选技术，允许从心室下区（SVZ）的主要神经发生群体的前瞻性纯化，我们证明了4个月大的年轻成年小鼠成年神经发生的早期下降与祖细胞的显著损失。激活的和静止的NSC池保持稳定长达12个月，激活的NSCs的增殖状态已经改变了6个月，由于G1的特异性延长导致细胞周期的整体延长。2月龄和6月龄小鼠活化的NSCs的全基因组分析进一步揭示了不同的转录组学和分子特征，以及TGFβ信号通路的调节。我们的微阵列研究构成了一个令人信服的鉴定新的分子参与者和信号通路调节成人神经发生及其早期修改。
Although neural stem cells (NSCs) sustain continuous neurogenesis throughout the adult lifespan of mammals, they progressively exhibit proliferation defects that contribute to a sharp reduction in subventricular neurogenesis during aging. However, little is known regarding the early age-related events in neurogenic niches. Using a fluorescence-activated cell sorting technique that allows for the prospective purification of the main neurogenic populations from the subventricular zone (SVZ), we demonstrated an early decline in adult neurogenesis with a dramatic loss of progenitor cells in 4 month-old young adult mice. Whereas the activated and quiescent NSC pools remained stable up to 12 months, the proliferative status of activated NSCs was already altered by 6 months, with an overall extension of the cell cycle resulting from a specific lengthening of G1. Whole genome analysis of activated NSCs from 2- and 6-month-old mice further revealed distinct transcriptomic and molecular signatures, as well as a modulation of the TGFβ signalling pathway. Our microarray study constitutes a cogent identification of new molecular players and signalling pathways regulating adult neurogenesis and its early modifications.