小柯机器人

英国剑桥大学Kathy K. Niakan小组的一项最新研究揭示了人、牛和小鼠胚胎中保守的滋养外胚层（TE）基序。该研究于2020年9月23日在线发表于国际学术期刊《自然》。

在本研究中，研究人员揭示了人、牛和小鼠胚胎中TE分离分子级联开启的进化保守性。在桑葚胚期，外层细胞获得顶基细胞极性，在非接触域表达非典型蛋白激酶C（aPKC）、细胞核表达Hippo信号通路效应因子并限制TE相关因子（如GATA3）的表达，这表明TE发育的起始。

此外，研究人员发现通过小分子药物或Trim-Away蛋白耗竭抑制aPKC会损害桑葚胚TE的起始。该比较胚胎学分析提供了对早期谱系分化基序的见解，并暗示了类似的机制可以开启动人、牛和小鼠胚胎的TE基序。

据了解，当前对哺乳动物早期着床前发育过程中细胞类型的认知主要基于在小鼠中的研究。谱系分化首先发生在桑葚胚时期，外部细胞开启TE胎盘祖细胞基序。在随后的发育阶段内部细胞产生内部细胞团、胚胎固有前体细胞和卵黄囊。最近研究揭示的基因表达分析表明，调节小鼠早期谱系发育的机制可能在其他哺乳动物中有所不同，例如人和牛。

附：英文原文

Title: Initiation of a conserved trophectoderm program in human, cow and mouse embryos

Author: Claudia Gerri, Afshan McCarthy, Gregorio Alanis-Lobato, Andrej Demtschenko, Alexandre Bruneau, Sophie Loubersac, Norah M. E. Fogarty, Daniel Hampshire, Kay Elder, Phil Snell, Leila Christie, Laurent David, Hilde Van de Velde, Ali A. Fouladi-Nashta, Kathy K. Niakan

Issue&Volume: 2020-09-23

Abstract: Current understandings of cell specification in early mammalian pre-implantation development are based mainly on mouse studies. The first lineage differentiation event occurs at the morula stage, with outer cells initiating a trophectoderm (TE) placental progenitor program. The inner cell mass arises from inner cells during subsequent developmental stages and comprises precursor cells of the embryo proper and yolk sac1. Recent gene-expression analyses suggest that the mechanisms that regulate early lineage specification in the mouse may differ in other mammals, including human2,3,4,5 and cow6. Here we show the evolutionary conservation of a molecular cascade that initiates TE segregation in human, cow and mouse embryos. At the morula stage, outer cells acquire an apical–basal cell polarity, with expression of atypical protein kinase C (aPKC) at the contact-free domain, nuclear expression of Hippo signalling pathway effectors and restricted expression of TE-associated factors such as GATA3, which suggests initiation of a TE program. Furthermore, we demonstrate that inhibition of aPKC by small-molecule pharmacological modulation or Trim-Away protein depletion impairs TE initiation at the morula stage. Our comparative embryology analysis provides insights into early lineage specification and suggests that a similar mechanism initiates a TE program in human, cow and mouse embryos.

DOI: 10.1038/s41586-020-2759-x

Source: https://www.nature.com/articles/s41586-020-2759-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：69.504
官方网址：http://www.nature.com/
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