美国德克萨斯大学西南医学中心Jun Wu研究小组发现，细胞竞争构成了种间嵌合的障碍。2021年1月28日，国际知名学术期刊《自然》在线发表了这一成果。
研究人员开发了一种种间多能干细胞（PSC）共培养策略，并揭示了物种之间细胞竞争的新模式。种间PSC竞争发生在原始但并非初始的多能性中，且似乎是发生在进化距离较远的物种之间。通过比较转录组分析，研究人员发现与NF-κB信号通路相关的基因在失败的人类细胞中被上调。人类细胞中NF-κB复合物的核心成分（P65）和上游调节子（MYD88）的遗传失活可以克服人-小鼠PSC竞争，从而改善早期小鼠胚胎中的人类细胞存活和嵌合现象。
这项研究发现了细胞竞争的新范式，为研究哺乳动物早期发育过程中竞争性细胞相互作用的进化保守机制铺平了道路。抑制种间PSC竞争可能会促进动物体内人体组织的生成。
据介绍，细胞竞争需要一种保守的适应性感知过程，在此过程中，适应型细胞能够消除相邻的不太适合的活细胞。有研究人员提出将细胞竞争作为一种监测机制，以确保正常发育和组织稳态，并且还提出将其作为种间嵌合现象的障碍。然而，迄今为止，由于缺乏体外模型，目前尚未在早期发育期间的种间环境中研究细胞竞争。
附：英文原文
Title: Cell Competition Constitutes a Barrier for Interspecies Chimerism
Author: Canbin Zheng, Yingying Hu, Masahiro Sakurai, Carlos A. Pinzon-Arteaga, Jie Li, Yulei Wei, Daiji Okamura, Benjamin Ravaux, Haley Rose Barlow, Leqian Yu, Hai-Xi Sun, Elizabeth H. Chen, Ying Gu, Jun Wu
Issue&Volume: 2021-01-28
Abstract: Cell competition entails a conserved fitness-sensing process during which fitter cells eliminate neighboring less-fit but viable cells1. Cell competition has been proposed as a surveillance mechanism to ensure normal development and tissue homeostasis, and has also been suggested to act as a barrier to interspecies chimerism2. To date, however, cell competition has not been studied in an interspecies context during early development due to lack of an in vitro model. Here, we developed an interspecies pluripotent stem cell (PSC) co-culture strategy and uncovered a previously unknown mode of cell competition between species. Interspecies PSC competition occurred in primed but not nave pluripotency and seemingly between evolutionarily distant species. Through comparative transcriptome analysis, we found genes related to the NF-κB signaling pathway, among others, were upregulated in loser human cells. Genetic inactivation of a core component (P65) and an upstream regulator (MYD88) of the NF-κB complex in human cells could overcome human-mouse PSC competition, thereby improving human cell survival and chimerism in early mouse embryos. Our study discovers a new paradigm of cell competition and paves the way for studying evolutionarily conserved mechanisms underlying competitive cell interaction during early mammalian development. Suppressing interspecies PSC competition may facilitate the generation of human tissues in animals.
DOI: 10.1038/s41586-021-03273-0
Source: https://www.nature.com/articles/s41586-021-03273-0
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/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
