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Multidimensional Chromatin Regulation of Cell Lineage Differentiation in a Metazoan Embryo
bioRxiv - Developmental Biology Pub Date : 2020-05-19 , DOI: 10.1101/2020.05.18.101584
Zhiguang Zhao , Rong Fan , Weina Xu , Yangyang Wang , Xuehua Ma , Zhuo Du

How chromatin dictates cell differentiation is an intriguing question in developmental biology. Here, a reporter gene integrated throughout the genome was used as a sensor to map the chromatin activity landscape in lineage-resolved cells during C. elegans embryogenesis. Single-cell analysis of chromatin dynamics across critical dimensions of cell differentiation was performed, including lineage, tissue, and symmetry. During lineage progression, chromatin gradually diversifies in general and exhibits switch-like changes following specific cell division, which is predictive of anterior-posterior fate asymmetry. Upon tissue differentiation, chromatin of cells from distinct lineages converge to tissue-specific states but retain memory of each cell's lineage history, which contributes to intra-tissue heterogeneity. However, cells with a morphologically left-right symmetric organization utilize a predetermination chromatin strategy to program analogous regulatory states in early progenitor cells. Additionally, chromatin co-regulation drives the functional coordination of the genome. Collectively, this work reveals the role of multidimensional chromatin regulation in cell differentiation.

中文翻译:

后生胚胎细胞谱系分化的多维染色质调控

染色质如何决定细胞分化是发育生物学中一个有趣的问题。在这里,整合在整个基因组中的报告基因被用作传感器,以绘制线虫胚胎发生过程中谱系分辨细胞中的染色质活性图。进行了跨细胞分化关键维度的染色质动力学的单细胞分析,包括谱系,组织和对称性。在沿袭进程中,染色质总体上逐渐多样化并在特定细胞分裂后表现出类似开关的变化,这预示着前后命运的不对称性。在组织分化后,来自不同谱系的细胞的染色质会聚到组织特定状态,但保留每个细胞谱系历史的记忆,这有助于组织内异质性。然而,具有左右对称形态的细胞利用预定的染色质策略来编程早期祖细胞中的类似调控状态。另外,染色质共调控驱动基因组的功能协调。总的来说,这项工作揭示了多维染色质调控在细胞分化中的作用。
更新日期:2020-05-19
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