Single-cell transcriptomics reveals gene signatures and alterations associated with aging in distinct neural stem/progenitor cell subpopulations.
Single-cell transcriptomics reveals gene signatures and alterations associated with aging in distinct neural stem/progenitor cell subpopulations.
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单细胞转录组学揭示了不同神经干/祖细胞亚群中与衰老相关的基因特征和改变
DOI：
10.1007/s13238-017-0450-2
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发表时间：
2018-04
期刊：
影响因子：
21.1
通讯作者：
Sun YE
中科院分区：
文献类型：
--
作者：
Shi Z;Geng Y;Liu J;Zhang H;Zhou L;Lin Q;Yu J;Zhang K;Liu J;Gao X;Zhang C;Yao Y;Zhang C;Sun YE
与衰老相关的认知能力下降与神经干/祖细胞（NSC/NPC）活性减弱有关，表现为增殖减少、产生神经元的倾向降低和向星形胶质细胞分化增加。虽然基因转录的变化客观地揭示了经历各种生物过程的细胞的分子改变，但对NSC/NPC衰老的分子机制的研究一直面临着脑细胞组成的巨大异质性和NSC/NPC所在的复杂细胞微环境。此外，脑NSC/NPC本身并不是一个同质的群体，这使得揭示NSC/NPC亚型特异性衰老机制变得更加困难。在这里，使用年轻和老年小鼠前脑室管膜和室管膜下区域的基于群体的和单细胞转录组分析以及全面的“大数据”处理，我们报告了NSC/NPC驻留在老年大脑中的相当炎症的环境中，这可能有助于星形胶质细胞与神经元的分化偏向。此外，单细胞转录组分析显示，不同年龄的NSC/NPC亚群，虽然都有减少的细胞增殖，使用不同的基因转录程序来调节细胞周期的年龄依赖性下降。有趣的是，细胞增殖能力的变化不受炎性细胞因子的影响，但可能由细胞内在机制引起。Erk/Mapk通路似乎关键地参与调节NSC/NPC进行克隆扩增的能力的年龄依赖性变化。总之，这项研究是第一个使用基于群体和单细胞的转录组分析来揭示不同NSC/NPC及其微环境在大脑老化背景下的分子相互作用的例子。
Aging associated cognitive decline has been linked to dampened neural stem/progenitor cells (NSC/NPCs) activities manifested by decreased proliferation, reduced propensity to produce neurons, and increased differentiation into astrocytes. While gene transcription changes objectively reveal molecular alterations of cells undergoing various biological processes, the search for molecular mechanisms underlying aging of NSC/NPCs has been confronted by the enormous heterogeneity in cellular compositions of the brain and the complex cellular microenvironment where NSC/NPCs reside. Moreover, brain NSC/NPCs themselves are not a homogenous population, making it even more difficult to uncover NSC/NPC sub-type specific aging mechanisms. Here, using both population-based and single cell transcriptome analyses of young and aged mouse forebrain ependymal and subependymal regions and comprehensive “big-data” processing, we report that NSC/NPCs reside in a rather inflammatory environment in aged brain, which likely contributes to the differentiation bias towards astrocytes versus neurons. Moreover, single cell transcriptome analyses revealed that different aged NSC/NPC subpopulations, while all have reduced cell proliferation, use different gene transcription programs to regulate age-dependent decline in cell cycle. Interestingly, changes in cell proliferation capacity are not influenced by inflammatory cytokines, but likely result from cell intrinsic mechanisms. The Erk/Mapk pathway appears to be critically involved in regulating age-dependent changes in the capacity for NSC/NPCs to undergo clonal expansion. Together this study is the first example of using population and single cell based transcriptome analyses to unveil the molecular interplay between different NSC/NPCs and their microenvironment in the context of the aging brain.
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DOI：
10.1073/pnas.0710000105
发表时间：
2008-01-22
影响因子：
11.1
作者：
Coskun, Volkan;Wu, Hao;Sun, Yi E.
通讯作者：
Sun, Yi E.
影响因子：
56.9
作者：
Bonni, A;Sun, Y;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
5.3
作者：
Maslov, AY;Barone, TA;Pruitt, SC
通讯作者：
Pruitt, SC
影响因子：
48
作者：
Picelli, Simone;Bjorklund, Asa K.;Sandberg, Rickard
通讯作者：
Sandberg, Rickard
影响因子：
5.3
作者：
Satoh, Yasushi;Kobayashi, Yasushi;Kazama, Tomiei
通讯作者：
Kazama, Tomiei