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Publication : Contractile fibroblasts form a transient niche for the branching mammary epithelium.

First Author  Sumbal J Year  2025
Journal  Nat Commun Volume  16
Issue  1 Pages  8576
PubMed ID  41022819 Mgi Jnum  J:373788
Mgi Id  MGI:8252056 Doi  10.1038/s41467-025-63612-x
Citation  Sumbal J, et al. (2025) Contractile fibroblasts form a transient niche for the branching mammary epithelium. Nat Commun 16(1):8576
abstractText  Fibroblasts are stromal cells found in connective tissue that are critical for organ development, tissue homeostasis and pathology. Single-cell transcriptomic analyses have revealed a high level of inter- and intra-organ heterogeneity of fibroblasts. However, the functional implications and lineage relations of different fibroblast subtypes remained unexplored, especially in the mammary gland. Here, we provide a comprehensive characterization of pubertal mouse mammary fibroblasts, through single-cell RNA sequencing, spatial mapping, functional assays, and in vivo lineage tracing. We unravel a transient niche-forming population of specialized contractile fibroblasts that exclusively localize around the tips of the growing mammary epithelium and are recruited from preadipocytes in the surrounding fat pad stroma. Using organoid-fibroblast co-cultures we reveal that different fibroblast populations can acquire contractile features when in direct contact with the epithelium, promoting organoid branching. The detailed in vivo characterization of these specialized cells and their lineage history provides insights into fibroblast heterogeneity and implicates their importance for creating a signalling niche during mouse mammary gland development.
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