Lgr5+ telocytes are a signaling source at the intestinal villus tip.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
22 04 2020
22 04 2020
Historique:
received:
10
12
2019
accepted:
24
03
2020
entrez:
24
4
2020
pubmed:
24
4
2020
medline:
1
8
2020
Statut:
epublish
Résumé
The intestinal epithelium is a structured organ composed of crypts harboring Lgr5+ stem cells, and villi harboring differentiated cells. Spatial transcriptomics have demonstrated profound zonation of epithelial gene expression along the villus axis, but the mechanisms shaping this spatial variability are unknown. Here, we combine laser capture micro-dissection and single cell RNA sequencing to uncover spatially zonated populations of mesenchymal cells along the crypt-villus axis. These include villus tip telocytes (VTTs) that express Lgr5, a gene previously considered a specific crypt epithelial stem cell marker. VTTs are elongated cells that line the villus tip epithelium and signal through Bmp morphogens and the non-canonical Wnt5a ligand. Their ablation is associated with perturbed zonation of enterocyte genes induced at the villus tip. Our study provides a spatially-resolved cell atlas of the small intestinal stroma and exposes Lgr5+ villus tip telocytes as regulators of the epithelial spatial expression programs along the villus axis.
Identifiants
pubmed: 32321913
doi: 10.1038/s41467-020-15714-x
pii: 10.1038/s41467-020-15714-x
pmc: PMC7176679
doi:
Substances chimiques
Lgr5 protein, mouse
0
Receptors, G-Protein-Coupled
0
Wnt-5a Protein
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1936Subventions
Organisme : NIDCR NIH HHS
ID : R35 DE026602
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK103147
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK085532
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
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