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生成 Piezo1-CreER 转基因小鼠,用于在体可视化和谱系追踪机械力应答细胞。

Generation of Piezo1-CreER transgenic mice for visualization and lineage tracing of mechanical force responsive cells in vivo.

机构信息

School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.

State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.

出版信息

Genesis. 2022 May;60(4-5):e23476. doi: 10.1002/dvg.23476. Epub 2022 May 2.

Abstract

Cells and tissues are exposed to a wide range of mechanical stimuli during development, tissue homeostasis, repair, and regeneration. Over the past few decades, mechanosensitive ion channels (MSCs), as force-sensing integral membrane proteins, have attracted great attention with regard to their structural dynamics and mechanics at the molecular level and functions in various cells. Piezo-type MSC component 1 (Piezo1) is a newly discovered MSC; it is inherently mechanosensitive. However, which type of cells express Piezo1 in vivo remains unclear. To detect and trace Piezo1-expressing cells, we generated and characterized a novel tamoxifen-inducible Cre knock-in mouse line, Piezo1-CreER, which expresses CreER recombinase under the control of the endogenous Piezo1 promoter. Using this genetic tool, we detected the expression of Piezo1 in various cell types at the embryonic, neonatal, and adult stages. Our data showed that Piezo1 was highly expressed in endothelial cells in all the three stages, while the Piezo1 expression in epithelial cells was dynamic during development and growth. In summary, we established a new genetic tool, Piezo1-CreER, to study Piezo1-expressing cells in vivo during development, injury response, and tissue repair and regeneration.

摘要

细胞和组织在发育、组织稳态、修复和再生过程中会受到广泛的机械刺激。在过去的几十年中,机械敏感离子通道(MSCs)作为力感应整合膜蛋白,其在分子水平上的结构动力学和力学以及在各种细胞中的功能引起了极大的关注。Piezo 型 MSC 成分 1(Piezo1)是一种新发现的 MSCs,它具有固有机械敏感性。然而,体内哪种类型的细胞表达 Piezo1 尚不清楚。为了检测和追踪 Piezo1 表达细胞,我们构建并鉴定了一种新型他莫昔芬诱导型 Cre 敲入小鼠系 Piezo1-CreER,该小鼠系在内源性 Piezo1 启动子的控制下表达 CreER 重组酶。利用这种遗传工具,我们在胚胎期、新生儿期和成年期检测了各种细胞类型中 Piezo1 的表达。我们的数据表明,Piezo1 在所有三个阶段都在血管内皮细胞中高度表达,而上皮细胞中的 Piezo1 表达在发育和生长过程中是动态的。总之,我们建立了一种新的遗传工具 Piezo1-CreER,用于研究体内发育、损伤反应和组织修复和再生过程中 Piezo1 表达细胞。

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