Contractile fibroblasts are recruited to growing mammary epithelium to support branching morphogenesis

Date

Apr 12, 2024

Time

11:00 AM - 12:00 PM

Speaker

Jakub Sumbal

Affiliation

Sorbonne Université, Paris, France & Faculty of Medicine, Masaryk University, Brno, Czech Republic

Language

en

Main Topic

Biologie

Host

Pavel Tomancak

Description

Fibroblasts are stromal cells of connective tissue, which are critical for organ development, homeostasis and disease. Single cell transcriptomic analyses have revealed a great level of inter- and intra-organ heterogeneity of fibroblasts, however, the functional implications and lineage relations of different fibroblast subtypes are unknown. In the mammary gland, fibroblasts support all stages of development, including branching morphogenesis, as well as the transition into breast cancer. Here we characterized pubertal mammary fibroblasts using single cell RNA sequencing, spatial mapping and in vivo lineage tracing and discovered a transient niche-forming population of contractile fibroblasts that specifically localize around growing epithelium after being recruited from the surrounding fat pad. Using functional organoid experiments we revealed that fibroblast contractility is needed for epithelial morphogenesis and that different fibroblast populations are activated by contact with the epithelium to support its morphogenesis. In summary, our detailed characterization brings new insight into mammary fibroblast heterogeneity, including functional relevance for epithelial morphogenesis and lineage hierarchy during normal mammary gland development in mice.

Last modified: Apr 13, 2024, 7:40:06 AM