Single-cell dynamics of chromatin activity during cell lineage differentiation in Caenorhabditis elegans embryos.

Single-cell dynamics of chromatin activity during cell lineage differentiation in Caenorhabditis elegans embryos.
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秀丽隐杆线虫胚胎细胞谱系分化过程中染色质活性的单细胞动力学

DOI:
10.15252/msb.202010075
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发表时间:
2021-04
影响因子:
9.9
通讯作者:
Du Z
Du Z
中科院分区:
生物学1区
文献类型:
--
作者:
Zhao Z;Fan R;Xu W;Kou Y;Wang Y;Ma X;Du Z

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阐明协调胚胎发生的染色质动力学是发育生物学的一个基本问题。在这里,我们利用表达的位置效应作为染色质活性的指标,并推断出秀丽隐杆线虫早期胚胎发生期间每个谱系细胞的染色质活性景观。系统级分析表明,染色质活性区分细胞状态并与早期胚胎的命运模式相关。随着细胞谱系的展开,染色质活性以谱系依赖性方式多样化,伴随前后命运不对称的开关样变化以及在不同细胞谱系中建立的特征景观。在组织分化时,来自不同谱系的细胞染色质根据组织类型汇聚,但保留了谱系历史的稳定记忆,从而导致组织细胞内的异质性。然而,以左右对称模式组织的细胞的染色质景观在早期祖细胞中被预先确定为类似的,以便预设等效状态。最后,全基因组分析识别出许多表现出一致染色质活性变化的区域,这些变化介导分化过程中功能相关基因的共同调节。总的来说,我们的研究揭示了单细胞水平染色质活性的发育和基因组动力学。本研究基于单细胞谱系追踪和活细胞成像,研究了秀丽隐杆线虫胚胎发生过程中局部染色质环境对报告基因表达的影响。
Elucidating the chromatin dynamics that orchestrate embryogenesis is a fundamental question in developmental biology. Here, we exploit position effects on expression as an indicator of chromatin activity and infer the chromatin activity landscape in every lineaged cell during Caenorhabditis elegans early embryogenesis. Systems‐level analyses reveal that chromatin activity distinguishes cellular states and correlates with fate patterning in the early embryos. As cell lineage unfolds, chromatin activity diversifies in a lineage‐dependent manner, with switch‐like changes accompanying anterior–posterior fate asymmetry and characteristic landscapes being established in different cell lineages. Upon tissue differentiation, cellular chromatin from distinct lineages converges according to tissue types but retains stable memories of lineage history, contributing to intra‐tissue cell heterogeneity. However, the chromatin landscapes of cells organized in a left–right symmetric pattern are predetermined to be analogous in early progenitors so as to pre‐set equivalent states. Finally, genome‐wide analysis identifies many regions exhibiting concordant chromatin activity changes that mediate the co‐regulation of functionally related genes during differentiation. Collectively, our study reveals the developmental and genomic dynamics of chromatin activity at the single‐cell level. This study investigates the influence of local chromatin environment on reporter gene expression during Caenorhabditis elegans embryogenesis, based on single‐cell lineage tracing and live‐cell imaging.
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