The MicroRNA Repertoire in Enteroendocrine Cells: Identification of miR-375 as a Potential Regulator of the Enteroendocrine Lineage

Endocrinology
Lina A KnudsenKristoffer L Egerod

Abstract

Micro-RNAs (miRNAs) are crucial for many biological processes, but their role in the enteroendocrine development and differentiation has been neglected due to the elusive nature of the enteroendocrine cells. However, transgenic mice expressing fluorescent reporter proteins under the control of promoters for Cck, Gpr41, and Lgr5, ie, two different enteroendocrine markers and a marker for the stem cells, now enables identification and FACS purification of enteroendocrine cells at different stages of their differentiation along the crypt-villus axis. Surprisingly few of the 746 analyzed miRNAs differed in their expression pattern between enteroendocrine and nonenteroendocrine cells of the gut mucosa and between enteroendocrine cells of the crypt versus the villus. Thus, only let-7g-3p, miR-7b-5p (miR-7b), and miR-375-3p (miR-375) were up-regulated in the enteroendocrine cells of both the crypt and villus compared with nonenteroendocrine cells, and in situ hybridization confirmed colocalization of miR-375 with the enteroendocrine cells. Finally, functional assays using miR-375 inhibitor and mimetic in organoid cultures revealed miR-375 as a potential regulator of the enteroendocrine lineage. Overexpression of miR-375 inhibited ente...Continue Reading

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