Col6a1⁺/CD201⁺mesenchymal cells regulate intestinal morphogenesis and homeostasis

Abstract

Intestinal mesenchymal cells encompass multiple subsets, whose origins, functions, and pathophysiological importance are still not clear. Here, we used the Col6a1Cre mouse, which targets telocytes and perivascular cells that can be further distinguished by the combination of the CD201, PDGFRα and αSMA markers. Lineage tracing revealed that telocytes originate from mesenchymal aggregates and are crucial for intestinal morphogenesis and patterning. Cell depletion experiments showed that Col6a1+/CD201+ telocytes regulate homeostatic enteroendocrine cell differentiation and epithelial proliferation. During acute colitis, they expressed an inflammatory and extracellular matrix remodeling gene signature, but they also retained their properties and topology. Notably, both in homeostasis and tissue regeneration, they were dispensable for normal organ architecture, as they were replaced by CD34+ mesenchymal cells, providing thus evidence for the plasticity potential of distinct mesenchymal populations in the intestine. Therefore, our results provide a comprehensive analysis of the identities, origin, and functional significance of colonic Col6a1Cre+ telocytes.