小柯机器人

小鼠原肠胚形成过程中的表观遗传调控功能
2020-07-30 14:38

德国马克斯·普朗克分子遗传学研究所Alexander Meissner团队揭示了小鼠原肠胚形成的表观遗传调节功能。这一研究成果在线发表在2020年7月29日的《自然》。

研究人员利用合子扰动和单细胞RNA测序平台相结合的方法来推进这些策略,在该平台中可以同时检测许多突变的小鼠胚胎,从而在一组十个必需调控因子中有效恢复形态学和转录信息。对多梳抑制复合物(PRC)核心组分1和2的深入分析表明PRC2在限制生殖细胞系中起协同但更加主导的作用。

此外,PRC突变体的表型出现在总体表观遗传和转录变化之后,这时处于发育早期原肠胚形成前。该实验可能有助于最终揭示具有相同遗传信息的细胞如何从单个全能细胞产生细胞多样性的完全定量图。

据了解,在个体发育过程中,细胞类型特异性转录因子和普遍存在的表观遗传机制相结合使得增殖细胞的命运受到限制,后者以环境依赖的方式利用广泛存在的组蛋白残基或核苷酸。这些调节因子的分子功能已广为人知,但复杂的突变表型阻碍了直接探究它们的作用,这些表型通常在原肠胚形成后出现。单细胞RNA测序和分析方法已经揭示了包括小鼠在内众多模式生物这一高度保守、动态的时期。

附:英文原文

Title: Epigenetic regulator function through mouse gastrulation

Author: Stefanie Grosswendt, Helene Kretzmer, Zachary D. Smith, Abhishek Sampath Kumar, Sara Hetzel, Lars Wittler, Sven Klages, Bernd Timmermann, Shankar Mukherji, Alexander Meissner

Issue&Volume: 2020-07-29

Abstract: During ontogeny, proliferating cells become restricted in their fate through the combined action of cell-type-specific transcription factors and ubiquitous epigenetic machinery, which recognizes universally available histone residues or nucleotides in a context-dependent manner1,2. The molecular functions of these regulators are generally well understood, but assigning direct developmental roles to them is hampered by complex mutant phenotypes that often emerge after gastrulation3,4. Single-cell RNA sequencing and analytical approaches have explored this highly conserved, dynamic period across numerous model organisms5,6,7,8, including mouse9,10,11,12,13,14,15,16,17,18. Here we advance these strategies using a combined zygotic perturbation and single-cell RNA-sequencing platform in which many mutant mouse embryos can be assayed simultaneously, recovering robust  morphological and transcriptional information across a panel of ten essential regulators. Deeper analysis of central Polycomb repressive complex (PRC) 1 and 2 components indicates substantial cooperativity, but distinguishes a dominant role for PRC2 in restricting the germline. Moreover, PRC mutant phenotypes emerge after gross epigenetic and transcriptional changes within the initial conceptus prior to gastrulation. Our experimental framework may eventually lead to a fully quantitative view of how cellular diversity emerges using an identical genetic template and from a single totipotent cell.

DOI: 10.1038/s41586-020-2552-x

Source: https://www.nature.com/articles/s41586-020-2552-x

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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