J 2024

Fibroblast-induced mammary epithelial branching depends on fibroblast contractility

SUMBAL, Jakub, Silvia FRE and Zuzana SUMBALOVÁ KOLEDOVÁ

Basic information

Original name

Fibroblast-induced mammary epithelial branching depends on fibroblast contractility

Authors

SUMBAL, Jakub (203 Czech Republic, belonging to the institution), Silvia FRE and Zuzana SUMBALOVÁ KOLEDOVÁ (703 Slovakia, belonging to the institution)

Edition

PLOS BIOLOGY, SAN FRANCISCO, PUBLIC LIBRARY SCIENCE, 2024, 1544-9173

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 9.800 in 2022

Organization unit

Faculty of Medicine

DOI

UT WoS

001142526300002

Keywords in English

mammary epithelial branching; fibroblasts

Tags

Tags

International impact, Reviewed
Změněno: 3/5/2024 14:05, Mgr. Tereza Miškechová

Abstract

V originále

Epithelial branching morphogenesis is an essential process in living organisms, through which organ-specific epithelial shapes are created. Interactions between epithelial cells and their stromal microenvironment instruct branching morphogenesis but remain incompletely understood. Here, we employed fibroblast-organoid or fibroblast-spheroid co-culture systems and time-lapse imaging to reveal that physical contact between fibroblasts and epithelial cells and fibroblast contractility are required to induce mammary epithelial branching. Pharmacological inhibition of ROCK or non-muscle myosin II, or fibroblast-specific knock-out of Myh9 abrogate fibroblast-induced epithelial branching. The process of fibroblast-induced branching requires epithelial proliferation and is associated with distinctive epithelial patterning of yes associated protein (YAP) activity along organoid branches, which is dependent on fibroblast contractility. Moreover, we provide evidence for the in vivo existence of contractile fibroblasts specifically surrounding terminal end buds (TEBs) of pubertal murine mammary glands, advocating for an important role of fibroblast contractility in branching in vivo. Together, we identify fibroblast contractility as a novel stromal factor driving mammary epithelial morphogenesis. Our study contributes to comprehensive understanding of overlapping but divergent employment of mechanically active fibroblasts in developmental versus tumorigenic programs. Epithelial branching morphogenesis is an essential process in living organisms, creating organ-specific epithelial shapes. This study uses time-lapse imaging of fibroblast co-cultures with epithelial organoids or spheroids to reveal that fibroblast contact and contractility are required for epithelial branching.

Links

GA23-04974S, research and development project
Name: Sdružený chemo-mechanický model normálního a nádorového mikroprostředí
Investor: Czech Science Foundation, Coupled chemo-mechanical model of normal and cancer microenvironment
MUNI/A/1301/2022, interní kód MU
Name: Zdroje pro tkáňové inženýrství 13
Investor: Masaryk University
MUNI/A/1398/2021, interní kód MU
Name: Zdroje pro tkáňové inženýrství 12 (Acronym: TissueEng 12)
Investor: Masaryk University
MUNI/G/1446/2018, interní kód MU
Name: Deciphering the mechanisms of mammary epithelial branched pattern formation through iterative biological and mathematical modelling
Investor: Masaryk University, INTERDISCIPLINARY - Interdisciplinary research projects
MUNI/G/1775/2020, interní kód MU
Name: ERK signaling code of epithelial morphogenesis and cancer
Investor: Masaryk University, INTERDISCIPLINARY - Interdisciplinary research projects
MUNI/IGA/1314/2021, interní kód MU
Name: Deciphering the fate and function of Notch1 positive mammary fibroblasts (Acronym: NOTCHFIB)
Investor: Masaryk University
MUNI/11/SUP/06/2022, interní kód MU
Name: Methods for measurement of mechanical forces on cell and tissue scale in organoids
Investor: Masaryk University, Start-up