Τίτλος:
Col6a1+/CD201+ mesenchymal cells regulate intestinal morphogenesis and homeostasis
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Intestinal mesenchymal cells encompass multiple subsets, whose origins, functions, and pathophysiological importance are still not clear. Here, we used the Col6a1Cre 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 Col6a1Cre mouse also targets mesenchymal aggregates that are crucial for intestinal morphogenesis and patterning, suggesting an ontogenic relationship between them and homeostatic PDGFRαhi telocytes. Cell depletion experiments in adulthood showed that Col6a1+/CD201+ mesenchymal cells regulate homeostatic enteroendocrine cell differentiation and epithelial proliferation. During acute colitis, they expressed an inflammatory and extracellular matrix remodelling gene signature, but they also retained their properties and topology. Notably, both in homeostasis and tissue regeneration, they were dispensable for normal organ architecture, while CD34+ mesenchymal cells expanded, localised at the top of the crypts, and showed increased expression of villous-associated morphogenetic factors, providing thus evidence for the plasticity potential of intestinal mesenchymal cells. Our results provide a comprehensive analysis of the identities, origin, and functional significance of distinct mesenchymal populations in the intestine. © 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Συγγραφείς:
Melissari, M.-T.
Henriques, A.
Tzaferis, C.
Prados, A.
Sarris, M.E.
Chalkidi, N.
Mavroeidi, D.
Chouvardas, P.
Grammenoudi, S.
Kollias, G.
Koliaraki, V.
Περιοδικό:
Cellular and Molecular Life Sciences (CMLS)
Εκδότης:
Springer Science and Business Media Deutschland GmbH
Λέξεις-κλειδιά:
Col6a1 protein, mouse; collagen type 6; endothelial protein C receptor; platelet derived growth factor alpha receptor; Procr protein, mouse, animal; cell differentiation; cell lineage; cell plasticity; cell proliferation; colitis; cytology; extracellular matrix; fibroblast; genetics; intestine; knockout mouse; mammalian embryo; mesenchymal stem cell; metabolism; mouse; pathology; physiology; regeneration, Animals; Cell Differentiation; Cell Lineage; Cell Plasticity; Cell Proliferation; Colitis; Collagen Type VI; Embryo, Mammalian; Endothelial Protein C Receptor; Extracellular Matrix; Fibroblasts; Intestines; Mesenchymal Stem Cells; Mice; Mice, Knockout; Receptor, Platelet-Derived Growth Factor alpha; Regeneration
DOI:
10.1007/s00018-021-04071-7
