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角蛋白是哺乳动物胚胎中不对称遗传的命运决定因素
2020-08-27 15:04

新加坡分子与细胞生物学研究所Nicolas Plachta课题组发现,角蛋白是哺乳动物胚胎中不对称遗传的命运决定因素。相关论文于2020年8月26日在线发表在《自然》杂志上。

研究人员发现,由角蛋白组装的中间丝可作为哺乳动物胚胎中不对称遗传的命运决定因素。与F-肌动蛋白或微管不同,角蛋白是细胞骨架的第一个主要组成部分,由于BAF染色质重塑复合体的异质性而引起细胞间显著变化。实时胚胎成像显示,角质蛋白在细胞分裂过程中被外层子细胞非对称遗传,其中它们稳定皮层来促进顶点极化和CDX2的YAP依赖性表达,从而确定了胚胎的第一个滋养外胚层细胞。
 
因此,这些数据揭示了一种机制,即在滋养外胚层和内部细胞团分离之前出现的细胞间异质性是通过差异性角蛋白调节来影响谱系命运,并确定发育时中间丝的早期功能。
 
据介绍,为了子宫着床,哺乳动物胚胎首先确定了两个细胞谱系:形成胎儿的多能内部细胞团和形成胎盘的外滋养外胚层。在许多生物中,不对称遗传的命运决定因素决定着谱系分化,但是在哺乳动物早期发育中却并非如此。
 
附:英文原文

Title: Keratins are asymmetrically inherited fate determinants in the mammalian embryo

Author: Hui Yi Grace Lim, Yanina D. Alvarez, Maxime Gasnier, Yiming Wang, Piotr Tetlak, Stephanie Bissiere, Hongmei Wang, Mat Biro, Nicolas Plachta

Issue&Volume: 2020-08-26

Abstract: To implant in the uterus, the mammalian embryo first specifies two cell lineages: the pluripotent inner cell mass that forms the fetus, and the outer trophectoderm layer that forms the placenta1. In many organisms, asymmetrically inherited fate determinants drive lineage specification2, but this is not thought to be the case during early mammalian development. Here we show that intermediate filaments assembled by keratins function as asymmetrically inherited fate determinants in the mammalian embryo. Unlike F-actin or microtubules, keratins are the first major components of the cytoskeleton that display prominent cell-to-cell variability, triggered by heterogeneities in the BAF chromatin-remodelling complex. Live-embryo imaging shows that keratins become asymmetrically inherited by outer daughter cells during cell division, where they stabilize the cortex to promote apical polarization and YAP-dependent expression of CDX2, thereby specifying the first trophectoderm cells of the embryo. Together, our data reveal a mechanism by which cell-to-cell heterogeneities that appear before the segregation of the trophectoderm and the inner cell mass influence lineage fate, via differential keratin regulation, and identify an early function for intermediate filaments in development. Keratins are determinants of cell fate during mammalian embryogenesis, and are distributed asymmetrically between daughter cells during cell division.

DOI: 10.1038/s41586-020-2647-4

Source: https://www.nature.com/articles/s41586-020-2647-4

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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