期刊
CELL REPORTS
卷 38, 期 10, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2022.110461
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资金
- France-BioImaging [ANR-10-INBS-04]
- ERC ZEBRATECTUM [311159]
- ARC [SFI20121205686]
- Schlumberger Foundation
- French National Research Agency (ANR) [ANR-15-CE13-0013-01]
- FRM Equipes [EQU201903007821]
- FSER (Schlumberger Foundation) [FSER20200211117]
- Labex DEEP [ANR-11-LBX-0044]
- University of Bristol
- Academy of Medical Sciences/Wellcome Trust/the Government Department of Business, Energy and Industrial Strategy/British Heart Foundation/Diabetes UK Springboard Award [SBF003/1170]
- Elizabeth Blackwell Institute for Health Research (University of Bristol)
- Wellcome Trust Institutional Strategic Support Fund [204813/Z/16/Z]
- PSL* Research University
- [ANR-11 BSV2 012 01]
- Agence Nationale de la Recherche (ANR) [ANR-15-CE13-0013] Funding Source: Agence Nationale de la Recherche (ANR)
- European Research Council (ERC) [311159] Funding Source: European Research Council (ERC)
Real-time in vivo imaging coupled with genetic lineage tracing reveals the regulatory role of Wnt/β-catenin signaling in the dynamics of mammary epithelial cells. Stabilization of β-catenin may lead to hyperplastic lesions and squamous transdifferentiation in the mammary epithelium.
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/i3-catenin signaling and the ensuing impact on the organization and differentiation of the mammary epithelium. This enables us to interrogate how Wnt/i3-catenin regulates the dynamics of distinct subpopulations of mammary epithelial cells in vivo and in real time. We show that 0-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, 0-catenin activation dictates a hair follicle/epidermal differentiation program independently of the targeted cell of origin.
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