Institut Curie, Laboratory of Genetics and Developmental Biology, PSL Research University, INSERM U934, CNRS UMR3215, 75248 Paris, France; School of Cellular and Molecular Medicine, University of Bristol, Biomedical Sciences Building, Bristol BS8 1TD, UK.
Institut Curie, Laboratory of Genetics and Developmental Biology, PSL Research University, INSERM U934, CNRS UMR3215, 75248 Paris, France.
Cell Rep. 2022 Mar 8;38(10):110461. doi: 10.1016/j.celrep.2022.110461.
Real-time in vivo imaging provides an essential window into the spatiotemporal cellular events contributing to tissue development and pathology. By coupling longitudinal intravital imaging with genetic lineage tracing, here we capture the earliest cellular events arising in response to active Wnt/β-catenin signaling and the ensuing impact on the organization and differentiation of the mammary epithelium. This enables us to interrogate how Wnt/β-catenin regulates the dynamics of distinct subpopulations of mammary epithelial cells in vivo and in real time. We show that β-catenin stabilization, when targeted to either the mammary luminal or basal epithelial lineage, leads to cellular rearrangements that precipitate the formation of hyperplastic lesions that undergo squamous transdifferentiation. These results enhance our understanding of the earliest stages of hyperplastic lesion formation in vivo and reveal that, in mammary neoplastic development, β-catenin activation dictates a hair follicle/epidermal differentiation program independently of the targeted cell of origin.
实时活体成像提供了一个重要的窗口，可以观察到参与组织发育和病理学的时空细胞事件。通过将纵向活体成像与遗传谱系追踪相结合，我们捕捉到了对活性 Wnt/β-catenin 信号的最早细胞反应，以及随后对乳腺上皮组织和分化的影响。这使我们能够研究 Wnt/β-catenin 如何在体内和实时调节不同亚群的乳腺上皮细胞的动态。我们表明，当将β-catenin 稳定化靶向到乳腺腔或基底上皮谱系时，会导致细胞重排，从而引发增生性病变的形成，并经历鳞状细胞转化。这些结果增强了我们对体内增生性病变形成的最早阶段的理解，并表明在乳腺肿瘤发生过程中，β-catenin 的激活决定了毛囊/表皮分化程序，而与靶细胞的起源无关。
