小柯机器人

膨胀-坍塌动态驱动肠道类器官中的模式化和形态发生
2021-04-30 15:46

近日,美国哈佛医学院Allon M. Klein及其课题组发现,膨胀-坍塌动态驱动肠道类器官中的模式化和形态发生。2021年4月28日,《细胞—干细胞》杂志在线发表了这项成果。

研究人员检查了控制干细胞区域(SCZ)大小的过程。并提高了肠道类器官培养物的生存能力和同质性,从而使多个类器官可以进行并行的长期延时成像。研究人员发现SCZ是由在离子通道介导的膨胀和机械敏感性压电家族通道控制下的分裂事件形成的。分裂是通过动态行为的定型模式发生的,这些模式的出芽和分化协调不同。成像和单细胞转录组学研究表明,膨胀驱动急性干细胞分化并诱导伸展反应性细胞状态,其特征为显著的转录变化,包括Piezo1的上调。

这些研究结果揭示了肠道上皮通过调节然后响应其机械状态而自组织的内在能力。

据悉,干细胞如何自我组织来形成结构化的组织是一个尚未解决的问题。肠类器官即使在没有空间结构化环境的情况下,也会产生典型大小的SCZ,从而提供了一种自组织模型。

附:英文原文

Title: Inflation-collapse dynamics drive patterning and morphogenesis in intestinal organoids

Author: Naren P. Tallapragada, Hailey M. Cambra, Tomas Wald, Samantha Keough Jalbert, Diana M. Abraham, Ophir D. Klein, Allon M. Klein

Issue&Volume: 2021-04-28

Abstract: How stem cells self-organize to form structured tissues is an unsolved problem. Intestinalorganoids offer a model of self-organization as they generate stem cell zones (SCZs)of typical size even without a spatially structured environment. Here we examine processesgoverning the size of SCZs. We improve the viability and homogeneity of intestinalorganoid cultures to enable long-term time-lapse imaging of multiple organoids inparallel. We find that SCZs are shaped by fission events under strong control of ionchannel-mediated inflation and mechanosensitive Piezo-family channels. Fission occursthrough stereotyped modes of dynamic behavior that differ in their coordination ofbudding and differentiation. Imaging and single-cell transcriptomics show that inflationdrives acute stem cell differentiation and induces a stretch-responsive cell statecharacterized by large transcriptional changes, including upregulation of Piezo1. Our results reveal an intrinsic capacity of the intestinal epithelium to self-organizeby modulating and then responding to its mechanical state.

DOI: 10.1016/j.stem.2021.04.002

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00159-4

 

Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:25.269
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx


本期文章:《细胞—干细胞》:Online/在线发表

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