The small and large intestine contain related mesenchymal subsets that derive from embryonic Gli1 + precursors.

Autor: Pærregaard SI; Department of Health Technology, Technical University of Denmark, Kemitorvet, 2800 Kgs, Lyngby, Denmark., Wulff L; Department of Health Technology, Technical University of Denmark, Kemitorvet, 2800 Kgs, Lyngby, Denmark., Schussek S; Department of Health Technology, Technical University of Denmark, Kemitorvet, 2800 Kgs, Lyngby, Denmark., Niss K; Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2200, Denmark., Mörbe U; Department of Health Technology, Technical University of Denmark, Kemitorvet, 2800 Kgs, Lyngby, Denmark., Jendholm J; Department of Health Technology, Technical University of Denmark, Kemitorvet, 2800 Kgs, Lyngby, Denmark., Wendland K; Immunology Section, Lund University, Lund, 221 84, Sweden., Andrusaite AT; Institute of Infection, immunity and Inflammation, University of Glasgow, Glasgow, Scotland, UK., Brulois KF; Laboratory of Immunology and Vascular Biology, Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA., Nibbs RJB; Institute of Infection, immunity and Inflammation, University of Glasgow, Glasgow, Scotland, UK., Sitnik K; Department of Health Technology, Technical University of Denmark, Kemitorvet, 2800 Kgs, Lyngby, Denmark., Mowat AM; Institute of Infection, immunity and Inflammation, University of Glasgow, Glasgow, Scotland, UK., Butcher EC; Laboratory of Immunology and Vascular Biology, Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA.; The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System and the Palo Alto Veterans Institute for Research (PAVIR), Palo Alto, CA, USA., Brunak S; Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2200, Denmark., Agace WW; Department of Health Technology, Technical University of Denmark, Kemitorvet, 2800 Kgs, Lyngby, Denmark. William.agace@med.lu.se.; Immunology Section, Lund University, Lund, 221 84, Sweden. William.agace@med.lu.se.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Apr 21; Vol. 14 (1), pp. 2307. Date of Electronic Publication: 2023 Apr 21.
DOI: 10.1038/s41467-023-37952-5
Abstrakt: The intestinal lamina propria contains a diverse network of fibroblasts that provide key support functions to cells within their local environment. Despite this, our understanding of the diversity, location and ontogeny of fibroblasts within and along the length of the intestine remains incomplete. Here we show that the small and large intestinal lamina propria contain similar fibroblast subsets that locate in specific anatomical niches. Nevertheless, we find that the transcriptional profile of similar fibroblast subsets differs markedly between the small intestine and colon suggesting region specific functions. We perform in vivo transplantation and lineage-tracing experiments to demonstrate that adult intestinal fibroblast subsets, smooth muscle cells and pericytes derive from Gli1-expressing precursors present in embryonic day 12.5 intestine. Trajectory analysis of single cell RNA-seq datasets of E12.5 and adult mesenchymal cells suggest that adult smooth muscle cells and fibroblasts derive from distinct embryonic intermediates and that adult fibroblast subsets develop in a linear trajectory from CD81 + fibroblasts. Finally, we provide evidence that colonic subepithelial PDGFRα hi fibroblasts comprise several functionally distinct populations that originate from an Fgfr2-expressing fibroblast intermediate. Our results provide insights into intestinal stromal cell diversity, location, function, and ontogeny, with implications for intestinal development and homeostasis.
(© 2023. The Author(s).)
Databáze: MEDLINE
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