Fibroblast-induced mammary epithelial branching depends on fibroblast contractility

SUMBAL, Jakub, Silvia FRE a Zuzana SUMBALOVÁ KOLEDOVÁ. Fibroblast-induced mammary epithelial branching depends on fibroblast contractility. PLOS BIOLOGY. SAN FRANCISCO: PUBLIC LIBRARY SCIENCE, 2024, roč. 22, č. 1, s. 1-29. ISSN 1544-9173. Dostupné z: https://dx.doi.org/10.1371/journal.pbio.3002093.

Základní údaje

Originální název

Fibroblast-induced mammary epithelial branching depends on fibroblast contractility

Autoři

SUMBAL, Jakub (203 Česká republika, domácí), Silvia FRE a Zuzana SUMBALOVÁ KOLEDOVÁ (703 Slovensko, domácí)

Vydání

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

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Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10601 Cell biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 9.800 v roce 2022

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1371/journal.pbio.3002093

UT WoS

001142526300002

Klíčová slova anglicky

mammary epithelial branching; fibroblasts

Štítky

14110517, rivok

Příznaky

Mezinárodní význam, Recenzováno

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Anotace

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.

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Návaznosti

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MUNI/G/1446/2018, interní kód MU	Název: Deciphering the mechanisms of mammary epithelial branched pattern formation through iterative biological and mathematical modelling Investor: Masarykova univerzita, Deciphering the mechanisms of mammary epithelial branched pattern formation through iterative biological and mathematical modelling, INTERDISCIPLINARY - Mezioborové výzkumné projekty
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