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首页> 美国卫生研究院文献>NPJ Systems Biology and Applications >Identification of an early cell fate regulator by detecting dynamics in transcriptional heterogeneity and co-regulation during astrocyte differentiation
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Identification of an early cell fate regulator by detecting dynamics in transcriptional heterogeneity and co-regulation during astrocyte differentiation

机译：通过检测星形胶质细胞分化过程中转录异质性和共调控的动力学来鉴定早期细胞命运调节剂

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摘要

There are an increasing number of reports that characterize the temporal behavior of gene expression at the single-cell level during cell differentiation. Despite accumulation of data describing the heterogeneity of biological responses, the dynamics of gene expression heterogeneity and its regulation during the differentiation process have not been studied systematically. To understand transcriptional heterogeneity during astrocyte differentiation, we analyzed single-cell transcriptional data from cells representing the different stages of astrocyte differentiation. When we compared the transcriptional variability of co-expressed genes between the undifferentiated and differentiated states, we found that there was significant increase in transcriptional variability in the undifferentiated state. The genes showing large changes in both “variability” and “correlation” between neural stem cells (NSCs) and astrocytes were found to be functionally involved in astrocyte differentiation. We determined that these genes are potentially regulated by Ascl1, a previously known oscillatory gene in NSCs. Pharmacological blockade of Ntsr2, which is transcriptionally co-regulated with Ascl1, showed that Ntsr2 may play an important role in the differentiation from NSCs to astrocytes. This study shows the importance of characterizing transcriptional heterogeneity and rearrangement of the co-regulation network between different cell states. It also highlights the potential for identifying novel regulators of cell differentiation that will further increase our understanding of the molecular mechanisms underlying the differentiation process.
机译：越来越多的报告描述了细胞分化过程中单细胞水平上基因表达的时间行为。尽管积累了描述生物学反应异质性的数据，但尚未系统地研究基因表达异质性的动力学及其在分化过程中的调控。为了了解星形胶质细胞分化过程中的转录异质性，我们分析了来自代表星形胶质细胞分化不同阶段的细胞的单细胞转录数据。当我们比较未分化状态和分化状态之间共表达基因的转录变异性时，我们发现未分化状态的转录变异性显着增加。发现神经干细胞（NSCs）和星形胶质细胞之间“变异性”和“相关性”均显示较大变化的基因在功能上参与星形胶质细胞的分化。我们确定这些基因可能受NSC中先前已知的振荡基因Ascl1调控。 Ntsr2的药理学封锁与Ascl1转录共调控，表明Ntsr2可能在从NSC分化为星形胶质细胞中起重要作用。这项研究表明了表征转录异质性和不同细胞状态之间共调节网络重排的重要性。它还强调了鉴定新型细胞分化调节剂的潜力，这将进一步增进我们对分化过程潜在分子机制的了解。

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