GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE151nnn/GSE151088/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE151088GEOGSEfalsemiR-375 Regulates Intestinal Crypt Cell Landscape, Proliferation, and Regenerative CapacityThe role of miRNAs in small intestinal epithelial homeostasis is under-explored. In this study, we discovered that miR-375 is among the most significantly enriched miRNAs in crypts, and in both slowly- and actively-cycling intestinal stem cells (ISCs). We then showed by multiple manipulations, including CRISPR/Cas9 editing, of mouse enteroids that miR-375 is strongly suppressed by Wnt signaling. Single cell RNA-seq analysis of jejunal crypt cells from miR-375 knockout (375-KO) mice revealed elevated numbers of tuft cells and increased expression of Wnt-pathway genes in ISCs. In accordance with these findings, 375-KO mice displayed significant improvement in the clearance of helminth infection and in the regenerative response to whole-body irradiation. The effects of miR-375 on gut epithelial survival and proliferation were further confirmed by ex vivo perturbations in murine enteroids and in vivo over-expression experiments in Drosophila stem/progenitor cells. Functional studies in enteroids revealed that suppression of miR-375 partially compensates for the effects of Yap1 inhibition on cell survival. Consistent with these results, we also find that miR-375 is significantly reduced in mouse and human intestinal tumors. Taken together, this study demonstrates that miR-375 is a master regulator of intestinal epithelial function, proliferation, and regenerative capacity.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 musculus