FOXL1+ TELOCYTES IN MOUSE COLON ORCHESTRATE ECM BIODYNAMICS AND WOUND REPAIR RESOLUTION

Recent studies identified FoxL1+-Telocytes (TCFoxL1+) as key players in gut epithelial-mesenchymal interactions impacting the microenvironment. Disruption of BMP-signaling in TCFoxL1+ alters the physical and cellular microenvironment leading to gut pathophysiology, suggesting a role for TCFoxL1+ in stromagenesis. However, profiling studies from whole tissue can be misleading when analyzing the specific contribution of TCFoxL1+. We performed an ex vivo deconstruction of control and BmpR1a△FoxL1+ colons, isolated the mesenchyme-enriched fractions and determined the protein composition of in vivo ECM to compare the microenvironment. Matrisomic analysis of mesenchyme fractions revealed modulations in ECM proteins with functions associated to innate immunity, epithelial wound healing and collagen network. These results show that TCFoxL1+ have a critical role in orchestrating the colon ECM biodynamics. Dysfunctional TCFoxL1+ reprogram the microenvironment driving the epithelium toward pathologies. This method allows to truthfully investigate how TCFoxL1+ impacts matrix dynamics leading to a comprehensive ECM profiling in diseases.