Spatially distinct epithelial and mesenchymal cell subsets along progressive lineage restriction in the branching embryonic mammary gland

How cells coordinate morphogenetic cues and fate specification during development remains a fundamental question in organogenesis. The mammary gland arises from multipotent stem cells (MaSCs), which are progressively replaced by unipotent progenitors by birth. However, the lack of specific markers f...

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Detalhes bibliográficos
Autores: Carabaña Gacía, Claudia, Sun, Wenjie, Veludo Ramos, Camila, Huyghe, Mathilde, Perkins, Meghan, Maillot, Aurelien, Journot, Robin, Hartani, Fatima, Faraldo, Marisa M., Lloyd-Lewis, Bethan, Fre, Silvia
Tipo de documento: artigo
Data de publicação:2024
País:España
Recursos:Universidad Europea (UEM)
Repositório:ABACUS. Repositorio de Producción Científica
Idioma:inglês
OAI Identifier:oai:abacus.universidadeuropea.com:11268/13131
Acesso em linha:http://hdl.handle.net/11268/13131
Access Level:Acceso aberto
Palavra-chave:Biología molecular
Embrión
Goal 3: Ensure healthy lives and promote well-being for all at all ages
Descrição
Resumo:How cells coordinate morphogenetic cues and fate specification during development remains a fundamental question in organogenesis. The mammary gland arises from multipotent stem cells (MaSCs), which are progressively replaced by unipotent progenitors by birth. However, the lack of specific markers for early fate specification has prevented the delineation of the features and spatial localization of MaSC-derived lineage-committed progenitors. Here, using single-cell RNA sequencing from E13.5 to birth, we produced an atlas of matched mouse mammary epithelium and mesenchyme and reconstructed the differentiation trajectories of MaSCs toward basal and luminal fate. We show that murine MaSCs exhibit lineage commitment just prior to the first sprouting events of mammary branching morphogenesis at E15.5. We identify early molecular markers for committed and multipotent MaSCs and define their spatial distribution within the developing tissue. Furthermore, we show that the mammary embryonic mesenchyme is composed of two spatially restricted cell populations, and that dermal mesenchyme-produced FGF10 is essential for embryonic mammary branching morphogenesis. Altogether, our data elucidate the spatiotemporal signals underlying lineage specification of multipotent MaSCs, and uncover the signals from mesenchymal cells that guide mammary branching morphogenesis.