Single-Cell Transcriptomic Analysis Defines Heterogeneity and Transcriptional Dynamics in the Adult Neural Stem Cell Lineage.
Single-Cell Transcriptomic Analysis Defines Heterogeneity and Transcriptional Dynamics in the Adult Neural Stem Cell Lineage.
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单细胞转录组分析定义了成年神经干细胞谱系中的异质性和转录动力学。
DOI：
10.1016/j.celrep.2016.12.060
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发表时间：
2017-01-17
期刊：
影响因子：
8.8
通讯作者：
Brunet A
中科院分区：
文献类型：
--
作者：
Dulken BW;Leeman DS;Boutet SC;Hebestreit K;Brunet A
成年哺乳动物大脑中的神经干细胞（NSC）是生成新神经元、少突胶质细胞和星形胶质细胞的储存库。在这里，我们使用单细胞 RNA 测序来表征成人 NSC 群体，并检查体内 NSC 群体的分子身份和异质性。我们发现 NSC 谱系中的细胞通过激活和分化过程连续存在。有趣的是，具有不同分子特征的罕见中间状态可以被识别并通过实验验证，并且我们的分析确定了这些 NSC 亚群的推定表面标记和关键细胞内调节因子。最后，利用单细胞分析的能力，我们进行荟萃分析来比较体内 NSC 和体外培养物、不同的荧光激活细胞分选策略和不同的神经源性生态位。这些数据为该领域提供了资源，并有助于对成人 NSC 谱系的综合理解。杜尔肯等人。对成年小鼠的神经干细胞 (NSC) 进行单细胞转录组学。他们使用机器学习来识别 NSC 谱系连续体中的稀有中间细胞，并与来自体外或体内 NSC 的其他单细胞转录组数据进行荟萃分析。
Neural stem cells (NSCs) in the adult mammalian brain serve as a reservoir for the generation of new neurons, oligodendrocytes, and astrocytes. Here we use single cell RNA-sequencing to characterize adult NSC populations and examine the molecular identities and heterogeneity of in vivo NSC populations. We find that cells in the NSC lineage exist on a continuum through the processes of activation and differentiation. Interestingly, rare intermediate states with distinct molecular profiles can be identified and experimentally validated, and our analysis identifies putative surface markers and key intracellular regulators for these subpopulations of NSCs. Finally, using the power of single cell profiling, we conduct a meta-analysis to compare in vivo NSCs and in vitro cultures, distinct fluorescent-activated cell sorting strategies, and different neurogenic niches. These data provide a resource for the field and contribute to an integrative understanding of the adult NSC lineage. Dulken et al. perform single cell transcriptomics on neural stem cells (NSCs) from adult mice. They use machine learning to identify rare intermediate cells in the continuum of the NSC lineage and perform a meta-analysis with other single cell transcriptomic data from in vitro or in vivo NSCs.