Mex3a Regulates Lgr5+ Stem Cell Maintenance in the Developing Intestinal Epithelium

    February 2020 in “ EMBO Reports ”
    Bruno Pereira, Ana Luísa Amaral, Alexandre Dias, Nuno Mendes, Vanesa Muncan, Ana R Silva, Chantal Thibert, A Radu, Leonor David, Valdemar Máximo, Gijs R. van den Brink, Marc Billaud, Raquel Almeida
    TLDR MEX3A is crucial for maintaining intestinal stem cells in mice.
    The study demonstrated that the RNA-binding protein MEX3A was essential for maintaining Lgr5+ intestinal stem cells (ISCs) during postnatal development. Using a Mex3a knockout mouse model, researchers found that the absence of MEX3A disrupted epithelial turnover and organoid maturation, leading to growth retardation and postnatal mortality. Transcriptomic analysis revealed that Mex3a deletion activated the PPARγ pathway, decreased Wnt signaling, and resulted in the loss of the Lgr5+ stem cell signature. High PPARγ signaling was shown to impair Lgr5+ ISC function, highlighting a new regulatory mechanism in ISCs that contributed to intestinal homeostasis. The study provided insights into the role of MEX3A in ISC regulation and its impact on intestinal development.
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