LGR5 controls extracellular matrix production by stem cells in the developing intestine.

Abstract:

:The Lgr5 receptor is a marker of intestinal stem cells (ISCs) that regulates Wnt/b-catenin signaling. In this study, phenotype analysis of knockin/knockout Lgr5-eGFP-IRES-Cre and Lgr5-DTReGFP embryos reveals that Lgr5 deficiency during Wnt-mediated cytodifferentiation results in amplification of ISCs and early differentiation into Paneth cells, which can be counteracted by in utero treatment with the Wnt inhibitor LGK974. 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 ISCs. 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 ISCs 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 ISCs in organoids, revealing a sophisticated regulatory process for Wnt signaling in ISCs.

journal_name

EMBO Rep

journal_title

EMBO reports

authors

Fernandez Vallone V,Leprovots M,Ribatallada-Soriano D,Gerbier R,Lefort A,Libert F,Vassart G,Garcia MI

doi

10.15252/embr.201949224

subject

Has Abstract

pub_date

2020-07-03 00:00:00

pages

e49224

issue

7

eissn

1469-221X

issn

1469-3178

journal_volume

21

pub_type

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