An inducible tricolor reporter mouse for simultaneous imaging of lysosomes, mitochondria and microtubules.
An inducible tricolor reporter mouse for simultaneous imaging of lysosomes, mitochondria and microtubules.
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一种可诱导的三色报告小鼠，用于同时对溶酶体、线粒体和微管进行成像。
DOI：
10.1101/2023.05.22.541817
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Chen,Jichao
中科院分区：
文献类型：
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作者：
Hutchison,Vera;Lynch,Anne;Gamez,AndrésMauricioGutierrez;Chen,Jichao
特定细胞类型使用相同的 DNA 蓝图会产生不同的细胞类型。这种多样性还必须通过相同亚细胞机器的差异部署来实现。然而，我们对天然组织中亚细胞机制的大小、分布和动力学及其与细胞多样性的联系的理解仍然有限。我们生成并表征了一种可诱导的三色报告小鼠，称为“万花筒”，用于以单细胞分辨率同时对任何细胞类型中的溶酶体、线粒体和微管进行成像。预期的亚细胞区室在培养物和组织中被标记，对细胞和生物体的活力没有影响。三色报告基因的定量和实时成像捕获了肺部细胞类型特异性细胞器特征和动力学，以及它们在仙台病毒感染后的变化。 Yap/Taz 突变肺上皮细胞经历加速板层体成熟，这是其分子缺陷的亚细胞表现。适用于所有亚细胞结构的综合报告工具箱有望改变我们对组织细胞生物学的理解。
Cell-type-specific use of the same DNA blueprint generates diverse cell types. Such diversity must also be executed via differential deployment of the same subcellular machinery. However, our understanding of the size, distribution, and dynamics of subcellular machinery in native tissues, and their connection to cellular diversity, remain limited. We generate and characterize an inducible tricolor reporter mouse, dubbed “kaleidoscope”, for simultaneous imaging of lysosomes, mitochondria and microtubules in any cell type and at a single cell resolution. The expected subcellular compartments are labeled in culture and in tissues with no impact on cellular and organismal viability. Quantitative and live imaging of the tricolor reporter captures cell-type-specific organelle features and kinetics in the lung, as well as their changes after Sendai virus infection. Yap/Taz mutant lung epithelial cells undergo accelerated lamellar body maturation, a subcellular manifestation of their molecular defects. A comprehensive toolbox of reporters for all subcellular structures is expected to transform our understanding of cell biology in tissues.