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LGR 5 controls extracellular matrix production by stem cells in the developing intestine
Author(s) -
Fernandez Vallone Valeria,
Leprovots Morgane,
RibatalladaSoriano Didac,
Gerbier Romain,
Lefort Anne,
Libert Frédérick,
Vassart Gilbert,
Garcia MarieIsabelle
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201949224
Subject(s) - humanities , library science , art , computer science
The Lgr5 receptor is a marker of intestinal stem cells ( ISC s) that regulates Wnt/b‐catenin signaling. In this study, phenotype analysis of knockin/knockout Lgr5‐ eGFP ‐ IRES ‐Cre and Lgr5‐ DTR e GFP embryos reveals that Lgr5 deficiency during Wnt‐mediated cytodifferentiation results in amplification of ISC s and early differentiation into Paneth cells, which can be counteracted by in utero treatment with the Wnt inhibitor LGK 974. Conditional ablation of Lgr5 postnatally, but not in adults, alters stem cell fate toward the Paneth lineage. Together, these in vivo studies suggest that Lgr5 is part of a feedback loop to adjust the Wnt tone in ISC s. Moreover, transcriptome analyses reveal that Lgr5 controls fetal ISC maturation associated with acquisition of a definitive stable epithelial phenotype, as well as the capacity of ISC s to generate their own extracellular matrix. Finally, using the ex vivo culture system, evidences are provided that Lgr5 antagonizes the Rspondin 2‐Wnt‐mediated response in ISC s in organoids, revealing a sophisticated regulatory process for Wnt signaling in ISC s.