Contractile fibroblasts form a transient niche for the branching mammary epithelium

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...

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Bibliographic Details
Published in:Nature communications Vol. 16; no. 1; pp. 8576 - 17
Main Authors: Sumbal, Jakub, Journot, Robin P., Attri, Kriti, Danek, Veronika, Merle, Candice, Faraldo, Marisa M., Sumbalova Koledova, Zuzana, Fre, Silvia
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 29.09.2025
Nature Publishing Group
Nature Portfolio
Subjects:
13
631/136/1660/1986
631/136/532/2139
631/80/84/2338
631/80/86/2368
Adipocytes - cytology
Adipocytes - metabolism
Animals
Cell Lineage
Cells
Coculture Techniques
Connective tissues
Contractility
Epithelial Cells - cytology
Epithelium
Epithelium - growth & development
Epithelium - metabolism
Female
Fibroblasts
Fibroblasts - cytology
Fibroblasts - metabolism
Fibroblasts - physiology
Gene sequencing
Heterogeneity
Homeostasis
Humanities and Social Sciences
Mammary gland
Mammary glands
Mammary Glands, Animal - cytology
Mammary Glands, Animal - growth & development
Mammary Glands, Animal - metabolism
Mice
Mice, Inbred C57BL
Morphogenesis
multidisciplinary
Organoids
Organoids - cytology
Organoids - metabolism
Preadipocytes
Science
Science (multidisciplinary)
Single-Cell Analysis
Smooth muscle
Stromal cells
Transcriptomics
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary: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. Fibroblasts represent a heterogenous cell population but how their differences reflect their plasticity and origin is not fully understood. Here, the authors map the origin and fate of a transient contractile fibroblast population that forms a niche supporting pubertal mammary gland branching and growth.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-025-63612-x