Paneth cells are antimicrobial peptide-secreting epithelial cells located at the bottom of the intestinal crypts of Lieberkühn. Crypts begin to form around day 7 of postnatal mice (P7), and Paneth cells usually appear within the first 2 weeks. Paneth cell dysfunction has been reported to correlate with Crohn’s disease-like inflammation, showing narrow crypts or loss of crypt architecture in mice. The morphology of dysfunctional Paneth cells is similar to that of a Paneth/goblet intermediate cell. However, it remains unclear whether the formation of the crypt is related to the maturation of Paneth cells. In this study, we investigated the histological changes in the mouse ileum postnatally and assessed the effect of the methyltransferase inhibitor on epithelium development using organoid culture. The morphological and functional maturation of Paneth cells occurred in the first 2 weeks and was accompanied by histone H3 lysine 27 (H3K27) trimethylation. Inhibition of H3K27 trimethylation suppressed crypt formation and Paneth cell maturation on organoids derived from ileum of early second postnatal mouse. Overall, our data show that post-transcriptional modification of histones, particularly H3K27 trimethylation, leads to the structural and functional maturation of Paneth cells during postnatal development.
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