MEX3A regulates Lgr5 + stem cell maintenance in the developing intestinal epithelium

• Type: Article in International Scientific Journal
• Date: 2020

Authors

Pereira, B (Author) Other; Amaral, AL (Author) Other; Dias, A (Author) Other; Mendes, N (Author) Other; Muncan, V (Author) Other; Silva, AR (Author) Other; Thibert, C (Author) Other; Radu, AG (Author) Other; David L (Author) FMUP; Maximo, V (Author) FMUP; van den Brink, GR (Author) Other; Billaud, M (Author) Other; Raquel Almeida (Author) FCUP

Journal

Title: EMBO Reports

Vol. 21

ISSN: 1469-221X

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 16 Citations

Scopus - 16 Citations

Other information

Authenticus ID: P-00R-S01

DOI: 10.15252/embr.201948938

Abstract (EN): Intestinal stem cells (ISCs) fuel the lifelong self-renewal of the intestinal tract and are paramount for epithelial repair. In this context, the Wnt pathway component LGR5 is the most consensual ISC marker to date. Still, the effort to better understand ISC identity and regulation remains a challenge. We have generated a Mex3a knockout mouse model and show that this RNA-binding protein is crucial for the maintenance of the Lgr5(+) ISC pool, as its absence disrupts epithelial turnover during postnatal development and stereotypical organoid maturation ex vivo. Transcriptomic profiling of intestinal crypts reveals that Mex3a deletion induces the peroxisome proliferator-activated receptor (PPAR) pathway, along with a decrease in Wnt signalling and loss of the Lgr5(+) stem cell signature. Furthermore, we identify PPAR gamma activity as a molecular intermediate of MEX3A-mediated regulation. We also show that high PPAR gamma signalling impairs Lgr5(+) ISC function, thus uncovering a new layer of post-transcriptional regulation that critically contributes to intestinal homeostasis.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 17