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通胀崩溃动力学驱动肠道类器官的模式形成和形态发生。

Inflation-collapse dynamics drive patterning and morphogenesis in intestinal organoids.

机构信息

Department of Systems Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.

Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA, USA; Department of Pediatrics and Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.

出版信息

Cell Stem Cell. 2021 Sep 2;28(9):1516-1532.e14. doi: 10.1016/j.stem.2021.04.002. Epub 2021 Apr 28.

DOI:10.1016/j.stem.2021.04.002
PMID:33915079
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8419000/
Abstract

How stem cells self-organize to form structured tissues is an unsolved problem. Intestinal organoids 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 processes governing the size of SCZs. We improve the viability and homogeneity of intestinal organoid cultures to enable long-term time-lapse imaging of multiple organoids in parallel. We find that SCZs are shaped by fission events under strong control of ion channel-mediated inflation and mechanosensitive Piezo-family channels. Fission occurs through stereotyped modes of dynamic behavior that differ in their coordination of budding and differentiation. Imaging and single-cell transcriptomics show that inflation drives acute stem cell differentiation and induces a stretch-responsive cell state characterized by large transcriptional changes, including upregulation of Piezo1. Our results reveal an intrinsic capacity of the intestinal epithelium to self-organize by modulating and then responding to its mechanical state.

摘要

干细胞如何自我组织形成结构组织是一个尚未解决的问题。肠类器官提供了自我组织的模型，因为即使没有空间结构环境，它们也能产生具有典型大小的干细胞区 (SCZ)。在这里，我们研究了控制 SCZ 大小的过程。我们提高了肠类器官培养物的存活率和均一性，从而能够在平行的多个类器官上进行长期延时成像。我们发现，SCZ 通过受离子通道介导的膨胀和机械敏感的 Piezo 家族通道强烈控制的裂变事件形成。裂变通过不同的芽生和分化协调的动态行为模式发生，这些模式具有不同的特征。成像和单细胞转录组学显示，膨胀驱动急性干细胞分化，并诱导一种对拉伸有反应的细胞状态，其特征是转录变化大，包括 Piezo1 的上调。我们的结果揭示了肠道上皮细胞通过调节其机械状态然后对其做出响应来自我组织的内在能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcbf/8419000/eedec98b6e62/nihms-1692667-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcbf/8419000/eb4c6fdfb735/nihms-1692667-f0002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcbf/8419000/d68d3029bd16/nihms-1692667-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcbf/8419000/abc0309542f3/nihms-1692667-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcbf/8419000/cd704ebc75d7/nihms-1692667-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcbf/8419000/d39922b5de2b/nihms-1692667-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcbf/8419000/eedec98b6e62/nihms-1692667-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcbf/8419000/eb4c6fdfb735/nihms-1692667-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcbf/8419000/4d793e29e81f/nihms-1692667-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcbf/8419000/d68d3029bd16/nihms-1692667-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcbf/8419000/abc0309542f3/nihms-1692667-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcbf/8419000/cd704ebc75d7/nihms-1692667-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcbf/8419000/d39922b5de2b/nihms-1692667-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcbf/8419000/eedec98b6e62/nihms-1692667-f0008.jpg

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