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• W3090533999 abstract "Summary The role of individual miRNAs in small intestinal (SI) epithelial homeostasis is under-explored. In this study, we discovered that miR-375 is among the most enriched miRNAs in intestinal crypts and stem cells (ISCs), especially facultative ISCs. We then showed by multiple manipulations, including CRISPR/Cas9 editing, that miR-375 is strongly suppressed by Wnt-signaling. Single-cell RNA-seq analysis of SI crypt-enriched cells from miR-375 knockout (375-KO) mice revealed elevated numbers of tuft cells and increased expression of pro-proliferative genes in ISCs. Accordingly, the genetic loss of miR-375 promoted resistance to helminth infection and enhanced the regenerative response to irradiation. The conserved effects of miR-375 were confirmed by gain-of-function studies in Drosophila midgut stem cells in vivo. Moreover, functional experiments in enteroids uncovered a regulatory relationship between miR-375 and Yap1 that controls cell survival. Finally, analysis of mouse model and clinical data revealed an inverse association between miR-375 levels and intestinal tumor development. Highlights miR-375 is one of the most enriched miRNAs in ISCs, especially facultative ISCs. miR-375 modifies tuft cell abundance and pro-proliferative gene expression in ISCs. Loss of miR-375 in mice enhances the host response to helminth infection and crypt regeneration. Mouse and human intestinal cancer are associated with reduced miR-375 expression. eTOC Blurb Sethupathy and colleagues show that miR-375 is a Wnt-responsive, ISC-enriched miRNA that serves as a break on intestinal crypt proliferation. They also show that miR-375 modulates tuft cell abundance and pro-proliferative gene expression in ISCs, that miR-375 loss enhances the host response to helminth infection as well as crypt regeneration post-irradiation, and its reduced expression is associated with intestinal cancer." @default.
• W3090533999 created "2020-10-08" @default.
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• W3090533999 date "2020-10-01" @default.
• W3090533999 modified "2023-10-14" @default.
• W3090533999 title "Single Cell Analysis Reveals Multi-faceted miR-375 Regulation of the Intestinal Crypt" @default.
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• W3090533999 doi "https://doi.org/10.1101/2020.10.01.321612" @default.
• W3090533999 hasPublicationYear "2020" @default.
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