Niche-associated Type IV collagen promotes GLP-1/Notch receptor activation in the C. elegans germline

Pier-Olivier Martel, Rustelle Janse van Vuuren, Julia Degrémont, Sarah Turmel-Couture, Armi M. Chaudhari, Eden Dologuele, Lucie Beaulieu, Alexandre Clouet and Patrick Narbonne ()
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Pier-Olivier Martel: Université du Québec à Trois-Rivières
Rustelle Janse van Vuuren: Université du Québec à Trois-Rivières
Julia Degrémont: Université de Montréal
Sarah Turmel-Couture: Université du Québec à Trois-Rivières
Armi M. Chaudhari: Université du Québec à Trois-Rivières
Eden Dologuele: Université du Québec à Trois-Rivières
Lucie Beaulieu: Université du Québec à Trois-Rivières
Alexandre Clouet: Université du Québec à Trois-Rivières
Patrick Narbonne: Université du Québec à Trois-Rivières

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Basement membranes are thin and dense proteinaceous layers that surround tissues to maintain their structure. With age, chronic inflammation typically stiffens this basement membrane through a phenomenon called fibrosis, which is reflected by increasing levels of the basement membrane’s main structural component, type IV collagen (COL IV). Tissue fibrosis and elevated Notch signalling are two co-occurring hallmarks of many inflammation-linked diseases, including cancer, but their in vivo relationship has not been clearly defined. Here we show that EMB-9/COL IV accumulation around the C. elegans germline stem cell niche promotes GLP-1/Notch receptor activation in germline stem cells. Moreover, we find that contrasting with previous beliefs, reducing GLP-1/Notch activity in vivo leads to a generalized dramatic increase in EMB-9/COL IV levels, and thereby promotes fibrosis. The generalized fibrosis that comes along with inflammaging may therefore act as a root cause for cancer by promoting Notch signalling, and perhaps other ligand-receptor interactions.

Date: 2025
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DOI: 10.1038/s41467-025-64394-y

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