小柯机器人

多组学解析单细胞分辨率的小鼠原肠运动
2019-12-12 19:47

英国剑桥大学Wolf ReikJohn C. MarioniOliver StegleStephen J. Clark等研究人员合作利用多组学技术解析了单细胞分辨率的小鼠原肠运动。20191211日,《自然》杂志在线发表了这项研究成果。

 

研究人员描绘了在小鼠胚胎原肠运动发生过程中染色质可及性、DNA甲基化和RNA表达的单细胞多组学图谱。多能性的初始退出与建立全局抑制性表观遗传景观相吻合,随后在原肠运动过程中出现了特定于谱系的表观遗传模式。

 

值得注意的是,位于中胚层和内胚层的细胞在增强子标记处经历了广泛的协同表观遗传重排,这是由TETten-eleven translocation)介导的去甲基化和随之而来的可及性增加所驱动的。相比之下,外胚层细胞的甲基化和可及性已在早期表皮细胞中建立。因此,在决定细胞命运之前,与每个胚层相关的调控元件在表观遗传被活化或被重塑,从而为初始胚层的分化提供了分子框架。

 

据介绍,原肠运动过程中三个主要胚层的形成是建立脊椎动物身体计划中必不可少的步骤,并且与主要的转录改变有关。全局性表观遗传重编程伴随着这些变化,但是表观基因组在调节早期细胞命运选择中的作用仍未得到解决,并且不同分子层面之间的协调性尚不清楚。

 

附:英文原文

Title: Multi-omics profiling of mouse gastrulation at single-cell resolution

Author: Ricard Argelaguet, Stephen J. Clark, Hisham Mohammed, L. Carine Stapel, Christel Krueger, Chantriolnt-Andreas Kapourani, Ivan Imaz-Rosshandler, Tim Lohoff, Yunlong Xiang, Courtney W. Hanna, Sebastien Smallwood, Ximena Ibarra-Soria, Florian Buettner, Guido Sanguinetti, Wei Xie, Felix Krueger, Berthold Gttgens, Peter J. Rugg-Gunn, Gavin Kelsey, Wendy Dean, Jennifer Nichols, Oliver Stegle, John C. Marioni, Wolf Reik

Issue&Volume: 2019-12-11

Abstract: Formation of the three primary germ layers during gastrulation is an essential step in the establishment of the vertebrate body plan and is associated with major transcriptional changes1,2,3,4,5. Global epigenetic reprogramming accompanies these changes6,7,8, but the role of the epigenome in regulating early cell-fate choice remains unresolved, and the coordination between different molecular layers is unclear. Here we describe a single-cell multi-omics map of chromatin accessibility, DNA methylation and RNA expression during the onset of gastrulation in mouse embryos. The initial exit from pluripotency coincides with the establishment of a global repressive epigenetic landscape, followed by the emergence of lineage-specific epigenetic patterns during gastrulation. Notably, cells committed to mesoderm and endoderm undergo widespread coordinated epigenetic rearrangements at enhancer marks, driven by ten-eleven translocation (TET)-mediated demethylation and a concomitant increase of accessibility. By contrast, the methylation and accessibility landscape of ectodermal cells is already established in the early epiblast. Hence, regulatory elements associated with each germ layer are either epigenetically primed or remodelled before cell-fate decisions, providing the molecular framework for a hierarchical emergence of the primary germ layers.

DOI: 10.1038/s41586-019-1825-8

Source: https://www.nature.com/articles/s41586-019-1825-8

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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