Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells.
Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells.
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DOI：
10.1038/s41467-017-01076-4
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发表时间：
2017-10-23
影响因子：
16.6
通讯作者：
van Oudenaarden A
中科院分区：
文献类型：
--
作者：
Semrau S;Goldmann JE;Soumillon M;Mikkelsen TS;Jaenisch R;van Oudenaarden A
小鼠胚胎干细胞(MESCs)在多能状态下的基因表达异质性已被越来越好地描述。相比之下，退出多能性和世系承诺还没有在单细胞水平上进行系统的研究。在这里，我们使用一种无偏见的单细胞转录学方法，测量了维甲酸诱导的mESC从多能性分化到谱系承诺的基因表达动态。我们发现，多能性的退出标志着谱系转变的开始，以及对谱系特定信号敏感性增加的短暂阶段。我们的研究揭示了这一阶段的几个转录特征，包括基因表达变异性的急剧增加和两类转录调控因子的顺序表达。综上所述，我们在单细胞水平上对多能性和谱系承诺的退出进行了全面的分析，这是通过分化提示的时机改善谱系操纵的潜在垫脚石。通过分化多能细胞对不同命运的承诺取决于外部和内部信号的整合。在这里，作者使用高时间分辨率的单细胞转录转录技术分析了小鼠胚胎干细胞进入维甲酸介导的分化过程。
Gene expression heterogeneity in the pluripotent state of mouse embryonic stem cells (mESCs) has been increasingly well-characterized. In contrast, exit from pluripotency and lineage commitment have not been studied systematically at the single-cell level. Here we measure the gene expression dynamics of retinoic acid driven mESC differentiation from pluripotency to lineage commitment, using an unbiased single-cell transcriptomics approach. We find that the exit from pluripotency marks the start of a lineage transition as well as a transient phase of increased susceptibility to lineage specifying signals. Our study reveals several transcriptional signatures of this phase, including a sharp increase of gene expression variability and sequential expression of two classes of transcriptional regulators. In summary, we provide a comprehensive analysis of the exit from pluripotency and lineage commitment at the single cell level, a potential stepping stone to improved lineage manipulation through timing of differentiation cues. Commitment to different fates by differentiating pluripotent cells depends upon integration of external and internal signals. Here the authors analyse the entry of mouse embryonic stem cells into retinoic acid-mediated differentiation using single cell transcriptomics with high temporal resolution.
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