biostudies-literatureMelissari MTFondation SanteStavros Niarchos FoundationEuropean Research CouncilHellenic Foundation for Research and InnovationEuropean Crohn's and Colitis Organisation1https://www.ebi.ac.uk/biostudies/studies/S-EPMC11073078biostudies-literatureUnknown79(1)Intestinal mesenchymal cells encompass multiple subsets, whose origins, functions, and pathophysiological importance are still not clear. Here, we used the Col6a1^Cre mouse, which targets distinct fibroblast subsets and perivascular cells that can be further distinguished by the combination of the CD201, PDGFRα and αSMA markers. Developmental studies revealed that the Col6a1^Cre mouse also targets mesenchymal aggregates that are crucial for intestinal morphogenesis and patterning, suggesting an ontogenic relationship between them and homeostatic PDGFRα^hi telocytes. Cell depletion experiments in adulthood showed that Col6a1⁺/CD201⁺ mesenchymal cells regulate homeostatic enteroendocrine cell differentiation and epithelial proliferation. DuCellular and molecular life sciences : CMLSCol6a1<sup>+</sup>/CD201<sup>+</sup> mesenchymal cells regulate intestinal morphogenesis and homeostasis.PMC110730781687340217Henriques ATzaferis CMelissari MTKoliaraki VChalkidi NPrados ASarris MEGrammenoudi SMavroeidi DChouvardas PKollias GfalseCol6a1<sup>+</sup>/CD201<sup>+</sup> mesenchymal cells regulate intestinal morphogenesis and homeostasis.Intestinal mesenchymal cells encompass multiple subsets, whose origins, functions, and pathophysiological importance are still not clear. Here, we used the Col6a1^Cre mouse, which targets distinct fibroblast subsets and perivascular cells that can be further distinguished by the combination of the CD201, PDGFRα and αSMA markers. Developmental studies revealed that the Col6a1^Cre mouse also targets mesenchymal aggregates that are crucial for intestinal morphogenesis and patterning, suggesting an ontogenic relationship between them and homeostatic PDGFRα^hi telocytes. Cell depletion experiments in adulthood showed that Col6a1⁺/CD201⁺ mesenchymal cells regulate homeostatic enteroendocrine cell differentiation and epithelial proliferation. Du2021-01-01T00:00:00Z2021 Dec2026-06-01T23:42:52.679Z2026-05-23T03:08:22.75ZS-EPMC110730783491025710.1007/s00018-021-04071-7