Budding epithelial morphogenesis driven by cell-matrix versus cell-cell adhesion.
Budding epithelial morphogenesis driven by cell-matrix versus cell-cell adhesion.
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DOI：
10.1016/j.cell.2021.05.015
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发表时间：
2021-07-08
期刊：
影响因子：
64.5
通讯作者：
Yamada KM
中科院分区：
文献类型：
--
作者：
Wang S;Matsumoto K;Lish SR;Cartagena-Rivera AX;Yamada KM
许多胚胎器官经历上皮形态发生以形成树状等级结构。然而，目前还不清楚是什么驱动了复层上皮的出芽和分支，例如在胚胎唾液腺和胰腺中。在这里，我们在单细胞分辨率下对小鼠胚胎唾液腺进行了活体器官成像，以揭示出芽形态发生是由不同上皮表面细胞片的扩张和折叠驱动的，其特征在于强细胞-基质粘附和弱细胞-细胞粘附。该上皮的单细胞转录组的分析揭示了这些细胞粘附差异的转录空间模式。然后，我们通过实验抑制E-钙粘蛋白表达并诱导工程细胞的3D球体培养物中的基底膜形成来合成重建出芽形态发生，这需要β1整合素介导的细胞基质粘附以成功出芽。因此，分层上皮出芽，分支形态发生的关键第一步，是由外周上皮细胞的强细胞-基质粘附和弱细胞-细胞粘附的整体组合驱动的。使用活器官成像和转录组学，以单细胞分辨率分析上皮形态发生为树状分级结构，并在工程细胞的3D球体培养物中合成重建早期步骤。
Many embryonic organs undergo epithelial morphogenesis to form tree-like hierarchical structures. However, it remains unclear what drives the budding and branching of stratified epithelia, such as in embryonic salivary gland and pancreas. Here, we performed live-organ imaging of mouse embryonic salivary glands at single-cell resolution to reveal that budding morphogenesis is driven by expansion and folding of a distinct epithelial surface cell sheet characterized by strong cell-matrix adhesions and weak cell-cell adhesions. Profiling of single-cell transcriptomes of this epithelium revealed spatial patterns of transcription underlying these cell adhesion differences. We then synthetically reconstituted budding morphogenesis by experimentally suppressing E-cadherin expression and inducing basement membrane formation in 3D spheroid cultures of engineered cells, which required β1 integrin-mediated cell-matrix adhesion for successful budding. Thus, stratified epithelial budding, the key first step of branching morphogenesis, is driven by an overall combination of strong cell-matrix adhesion and weak cell-cell adhesion by peripheral epithelial cells. Using live organ imaging and transcriptomics, epithelial morphogenesis into tree-like hierarchical structures was profiled at single-cell resolution and the early steps were synthetically reconstituted in 3D spheroid cultures of engineered cells.
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