Non-monotonic Changes in Progenitor Cell Behavior and Gene Expression during Aging of the Adult V-SVZ Neural Stem Cell Niche.
Non-monotonic Changes in Progenitor Cell Behavior and Gene Expression during Aging of the Adult V-SVZ Neural Stem Cell Niche.
复制标题
成年V-SVZ神经干细胞壁ne衰老期间，祖细胞行为和基因表达的非单调变化。
DOI：
10.1016/j.stemcr.2017.10.005
复制
发表时间：
2017-12-12
影响因子：
5.9
通讯作者：
Temple S
中科院分区：
文献类型：
--
作者：
Apostolopoulou M;Kiehl TR;Winter M;Cardenas De La Hoz E;Boles NC;Bjornsson CS;Zuloaga KL;Goderie SK;Wang Y;Cohen AR;Temple S
脑室-室下区（V-SVZ）的神经干细胞活性随着年龄的增长而下降，被认为是单向下降。然而，通过分析雄性小鼠在2、6、18和22月龄时的V-SVZ转录组，我们发现大多数随时间显著变化的基因呈现逆转趋势，在18月龄时表达量最大或最小。在体内，MASH1+祖细胞的数量和增殖在2 ~ 18个月期间减少，但在18 ~ 22个月期间增加。对944个V-SVZ细胞的时间推移谱系分析显示，在体外克隆中再现了与年龄相关的神经发生衰退。然而，激活的B型/ C型细胞克隆在2至18个月时分裂较慢，然后在22个月时出乎意料地更快，向A型神经母细胞的转变受损。我们的研究结果表明，V-SVZ的衰老涉及到祖细胞内编程的显著非单调变化，并且可以独立于衰老生态位观察到。衰老2、6、18、22月龄成人V-SVZ NSC生态位的RNA测序分析在体内，MASH1+细胞周期在18个月时最慢，但在22个月时恢复到2个月的速度。对分离的SVZ细胞的时间推移分析表明，年龄相关的变化是程序化的。Temple及其同事通过一项多时间点研究表明，成人V-SVZ中基因表达和细胞行为的年龄相关变化主要是非单调的。神经发生随着年龄的增长而减少，转运扩增祖细胞的数量和细胞分裂率在18个月前下降，然后在18 - 22个月间惊人地增加。此外，他们证明这些行为在克隆培养的单个祖细胞中重现，表明年龄相关的变化是程序化的，与生态位无关。
Neural stem cell activity in the ventricular-subventricular zone (V-SVZ) decreases with aging, thought to occur by a unidirectional decline. However, by analyzing the V-SVZ transcriptome of male mice at 2, 6, 18, and 22 months, we found that most of the genes that change significantly over time show a reversal of trend, with a maximum or minimum expression at 18 months. In vivo, MASH1+ progenitor cells decreased in number and proliferation between 2 and 18 months but increased between 18 and 22 months. Time-lapse lineage analysis of 944 V-SVZ cells showed that age-related declines in neurogenesis were recapitulated in vitro in clones. However, activated type B/type C cell clones divide slower at 2 to 18 months, then unexpectedly faster at 22 months, with impaired transition to type A neuroblasts. Our findings indicate that aging of the V-SVZ involves significant non-monotonic changes that are programmed within progenitor cells and are observable independent of the aging niche. RNA sequencing analysis of the adult V-SVZ NSC niche at 2, 6, 18, and 22 months During aging, most V-SVZ niche genes show max/min expression at 18 months In vivo MASH1+ cells cycle slowest at 18 months but at 22 months return to 2-month rate Time-lapse analyses of isolated SVZ cells show that age-associated changes are programmed Temple and colleagues show through a multi-time-point study that age-associated changes in gene expression and cell behavior in the adult V-SVZ are predominantly non-monotonic. While neurogenesis declines with aging, the number and cell division rate of transit-amplifying progenitor cells declines to 18 months and then surprisingly increases between 18 and 22 months. Furthermore, they demonstrate that these behaviors are recapitulated in single progenitor cells growing in clonal culture, indicating that age-associated changes are programmed and niche independent.
登录
查看更多内容
影响因子：
4.6
作者：
Daynac M;Morizur L;Chicheportiche A;Mouthon MA;Boussin FD
通讯作者：
Boussin FD
影响因子：
4.8
作者：
An, Sojin;Yeo, Kwon Joo;Song, Ji-Joon
通讯作者：
Song, Ji-Joon
影响因子：
2.7
作者：
Martynoga, B;Morrison, H;Mason, JO
通讯作者：
Mason, JO
影响因子：
5.3
作者：
Brill, Monika S.;Snapyan, Marina;Goetz, Magdalena
通讯作者：
Goetz, Magdalena
DOI：
10.1073/pnas.97.18.10101
发表时间：
2000-08-29
影响因子：
11.1
作者：
Alter, O;Brown, PO;Botstein, D
通讯作者：
Botstein, D