Fibroblast-induced mammary epithelial branching depends on fibroblast contractility
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F24%3A00135427" target="_blank" >RIV/00216224:14110/24:00135427 - isvavai.cz</a>
Result on the web
<a href="https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002093" target="_blank" >https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002093</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1371/journal.pbio.3002093" target="_blank" >10.1371/journal.pbio.3002093</a>
Alternative languages
Result language
angličtina
Original language name
Fibroblast-induced mammary epithelial branching depends on fibroblast contractility
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10601 - Cell biology
Result continuities
Project
<a href="/en/project/EF19_073%2F0016943" target="_blank" >EF19_073/0016943: Internal grant agency of Masaryk University</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
PLOS BIOLOGY
ISSN
1544-9173
e-ISSN
1545-7885
Volume of the periodical
22
Issue of the periodical within the volume
1
Country of publishing house
US - UNITED STATES
Number of pages
29
Pages from-to
1-29
UT code for WoS article
001142526300002
EID of the result in the Scopus database
2-s2.0-85182377750