Telomere length and human hippocampal neurogenesis.
Telomere length and human hippocampal neurogenesis.
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DOI：
10.1038/s41386-020-00863-w
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Powell TR
中科院分区：
文献类型：
--
作者：
Palmos AB;Duarte RRR;Smeeth DM;Hedges EC;Nixon DF;Thuret S;Powell TR
短端粒长度是年龄相关疾病的危险因素，但它也与海马体积减少，年龄相关的认知能力下降和精神疾病风险有关。目前的研究探讨了端粒缩短是否可能对认知功能和精神疾病的病理生理学的影响，通过其对成年海马神经发生的假设影响。我们模拟端粒缩短人海马祖细胞在体外使用一系列传代协议，模仿末端复制的问题。连续传代的祖细胞显示端粒较短（P ≤ 0.05），细胞增殖速率降低（P ≤ 0.001），细胞分化为神经元或神经胶质的能力无变化。RNA测序和基因集富集分析揭示了细胞衰老对与神经发生、端粒维持、细胞衰老和细胞因子产生相关的基因网络的影响。在我们的模型中，下调的转录物与调节认知功能的基因（P ≤ 1 × 10−5）以及精神分裂症（P ≤ 1 × 10−10）和双相情感障碍（P ≤ 0.005）的风险有显著重叠。总的来说，我们的研究结果表明，端粒缩短可能是一种调节人类海马祖细胞增殖能力的机制，这可能会影响人类认知功能和精神疾病的病理生理学。
Short telomere length is a risk factor for age-related disease, but it is also associated with reduced hippocampal volumes, age-related cognitive decline and psychiatric disorder risk. The current study explored whether telomere shortening might have an influence on cognitive function and psychiatric disorder pathophysiology, via its hypothesised effects on adult hippocampal neurogenesis. We modelled telomere shortening in human hippocampal progenitor cells in vitro using a serial passaging protocol that mimics the end-replication problem. Serially passaged progenitors demonstrated shorter telomeres (P ≤ 0.05), and reduced rates of cell proliferation (P ≤ 0.001), with no changes in the ability of cells to differentiate into neurons or glia. RNA-sequencing and gene-set enrichment analyses revealed an effect of cell ageing on gene networks related to neurogenesis, telomere maintenance, cell senescence and cytokine production. Downregulated transcripts in our model showed a significant overlap with genes regulating cognitive function (P ≤ 1 × 10−5), and risk for schizophrenia (P ≤ 1 × 10−10) and bipolar disorder (P ≤ 0.005). Collectively, our results suggest that telomere shortening could represent a mechanism that moderates the proliferative capacity of human hippocampal progenitors, which may subsequently impact on human cognitive function and psychiatric disorder pathophysiology.
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影响因子：
11
作者：
Hibar, D. P.;Westlye, L. T.;van Erp, T. G. M.;Rasmussen, J.;Leonardo, C. D.;Faskowitz, J.;Haukvik, U. K.;Hartberg, C. B.;Doan, N. T.;Agartz, I.;Dale, A. M.;Gruber, O.;Kraemer, B.;Trost, S.;Liberg, B.;Abe, C.;Ekman, C. J.;Ingvar, M.;Landen, M.;Fears, S. C.;Freimer, N. B.;Bearden, C. E.;Sprooten, E.;Glahn, D. C.;Pearlson, G. D.;Emsell, L.;Kenney, J.;Scanlon, C.;McDonald, C.;Cannon, D. M.;Almeida, J.;Versace, A.;Caseras, X.;Lawrence, N. S.;Phillips, M. L.;Dima, D.;Delvecchio, G.;Frangou, S.;Satterthwaite, T. D.;Wolf, D.;Houenou, J.;Henry, C.;Malt, U. F.;Boen, E.;Elvsashagen, T.;Young, A. H.;Lloyd, A. J.;Goodwin, G. M.;Mackay, C. E.;Bourne, C.;Bilderbeck, A.;Abramovic, L.;Boks, M. P.;van Haren, N. E. M.;Ophoff, R. A.;Kahn, R. S.;Bauer, M.;Pfennig, A.;Alda, M.;Hajek, T.;Mwangi, B.;Soares, J. C.;Nickson, T.;Dimitrova, R.;Sussmann, J. E.;Hagenaars, S.;Whalley, H. C.;McIntosh, A. M.;Thompson, P. M.;Andreassen, O. A.
通讯作者：
Andreassen, O. A.
影响因子：
3.7
作者：
Grodstein, Francine;van Oijen, Marieke;Irizarry, Michael C.;Rosas, H. Diana;Hyman, Bradley T.;Growdon, John H.;De Vivo, Immaculata
通讯作者：
De Vivo, Immaculata
影响因子：
14.9
作者：
Cawthon RM
通讯作者：
Cawthon RM
影响因子：
4.7
作者：
Chen, G;Rajkowska, G;Manji, HK
通讯作者：
Manji, HK
影响因子：
7.8
作者：
Chebel, Amel;Bauwens, Serge;Ffrench, Martine
通讯作者：
Ffrench, Martine