Biology subjects

Vassart, G.

Publications and source records attributed to Vassart, G..

3 recordsLinked to original sources

bioRxiv2024

An Lgr5-independent developmental lineage is involved in mouse intestinal regeneration

Collagenase/dispase treatment of intestinal tissue from adult mice generates cells growing in matrigel as stably replatable cystic spheroids in addition to differentiated organoids. Contrary to classical EDTA-derived organoids, these spheroids display poor intestinal differentiation and are independent of Rspondin/Noggin/EGF for growth. Their transcriptome resembles strikingly that of fetal intestinal spheroids, with downregulation of crypt base columnar cell (CBC) markers (Lgr5, Ascl2, Smoc2, Olfm4). In addition, they display upregulation of inflammatory and mesenchymal genetic programs, together with robust expression of YAP target genes. Lineage tracing, cell-sorting and single cell RNA sequencing experiments demonstrate that adult spheroid-generating cells belong to a hitherto undescribed developmental lineage, independent of Lgr5+ve CBCs, and are involved in regeneration of the epithelium following CBC ablation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=153 SRC="FIGDIR/small/584399v3_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@c8d67corg.highwire.dtl.DTLVardef@1799ca2org.highwire.dtl.DTLVardef@11a7d92org.highwire.dtl.DTLVardef@2a1c9b_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2023

THE OLFACTORY RECEPTOR Olfr78 REGULATES DIFFERENTIATION OF ENTEROCHROMAFFIN CELLS IN THE MOUSE COLON

The gastrointestinal epithelium constitutes a chemosensory system for microbiota-derived metabolites such as Short Chain Fatty Acids (SCFA). In this study, we investigated spatial distribution of Olfr78, one of the SCFA receptors, in the mouse intestine and studied the transcriptome of colon enteroendocrine cells expressing Olfr78. The receptor is principally detected in the enterochromaffin and L subtypes in the proximal and distal colon, respectively. Using the Olfr78-GFP and VilCre/Olfr78flox transgenic mouse lines, we reveal that loss of epithelial Olfr78 results in impaired enterochromaffin cell differentiation, blocking cells in an undefined secretory lineage state. This is accompanied by dysbiosis, characterized by an increased Firmicutes/Bacteroidetes ratio, as well as a less efficient antioxidant system in colon crypts. Using organoid cultures, we further show that maintenance of enterochromaffin cells involves activation of the Olfr78 receptor via the SCFA ligand acetate. Altogether, this work provides evidence that Olfr78 contributes to colon homeostasis by regulating enterochromaffin cell differentiation.

cell biology↗

bioRxiv2019

Lgr5 Controls Extracellular Matrix Production By Stem Cells In The Developing Intestine

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 revealed 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, altered stem cell fate towards 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 revealed that fetal ISCs generate their own extracellular matrix components, a property lost in adult ISCs, which adopt a definitive epithelialized phenotype and an inflammatory response signature. Absence of Lgr5 in fetal ISCs resulted in reduced extracellular matrix production and accelerated ISC maturation, indicating that Lgr5 regulates the ISC niche. Finally, evidences are provided that Rspondin 2 negatively regulates the pool of ISCs in organoids via Lgr5, revealing a sophisticated regulatory process for Wnt signaling in ISC.

developmental biology↗