RT Journal Article
SR Electronic
T1 Functional transcriptomics in diverse intestinal epithelial cell types reveals robust gut microbial sensitivity of microRNAs in intestinal stem cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 087882
DO 10.1101/087882
A1 Bailey C. E. Peck
A1 Amanda T. Mah
A1 Wendy A. Pitman
A1 Shengli Ding
A1 P. Kay Lund
A1 Praveen Sethupathy
YR 2016
UL http://biorxiv.org/content/early/2016/11/15/087882.abstract
AB Gut microbiota play an important role in regulating the development of the host immune system, metabolic rate, and at times, disease pathogenesis. The factors and mechanisms that mediate communication between microbiota and the intestinal epithelium are poorly understood. We provide novel evidence that microbiota may control intestinal epithelial stem cell (IESC) proliferation in part through microRNAs (miRNAs). We demonstrate that miRNA profiles differ dramatically across functionally distinct cell types of the mouse jejunal intestinal epithelium and that miRNAs respond to microbiota in a highly cell-type specific manner. Importantly, we also show that miRNAs in IESCs are more prominently regulated by microbiota compared to miRNAs in any other intestinal epithelial cell (IEC) subtype. We identify miR-375 as one miRNA that is significantly suppressed by the presence of microbiota in IESCs. Using a novel method to knockdown gene and miRNA expression ex vivo enteroids, we demonstrate that we can knockdown gene expression in Lgr5+ IESCs. Furthermore, when we knockdown miR-375 in IESCs, we observe significantly increased proliferative capacity. Understanding the mechanisms by which microbiota regulate miRNA expression in IESCs and other IEC subtypes will elucidate a critical molecular network that controls intestinal homeostasis and, given the heightened interest in miRNA-based therapies, may offer novel therapeutic strategies in the treatment of gastrointestinal diseases associated with altered IESC function.