miR-7 Modulates hESC Differentiation into Insulin-Producing Beta-like Cells and Contributes to Cell Maturation

Abstract

Human pluripotent stem cells retain the extraordinary capacity to differentiate into pancreatic beta cells. For this particular lineage, more effort is still required to stress the importance of developing an efficient, reproducible, easy, and cost-effective differentiation protocol to obtain more mature, homogeneous, and functional insulin-secreting cells. In addition, microRNAs (miRNAs) have emerged as a class of small non-coding RNAs that regulate many cellular processes, including pancreatic differentiation. Some miRNAs are known to be preferentially expressed in islets. Of note, miR-375 and miR-7 are two of the most abundant pancreatic miRNAs, and they are necessary for proper pancreatic islet development. Here we provide new insight into specific miRNAs involved in pancreatic differentiation. We found that miR-7 is differentially expressed during the differentiation of human embryonic stem cells (hESCs) into a beta cell-like phenotype and that its modulation plays an important role in generating mature pancreatic beta cells. This strategy may be exploited to optimize the potential for in vitro differentiation of hESCs into insulin-producing beta-like cells for use in preclinical studies and future clinical applications as well as the prospective uses of miRNAs to improve this process.

MicroRNA 7 Impairs Insulin Signaling and Regulates Aβ Levels through Posttranscriptional Regulation of the Insulin Receptor Substrate 2, Insulin Receptor, Insulin-Degrading Enzyme, and Liver X Receptor Pathway

“…In humans, the miR-7 family consists of three members (miR-7-1, miR-7-2, and miR-7-3) localized on human chromosomes 9, 15, and 19, respectively. miR-7 has been shown to regulate important aspects of pancreatic biology and functions, including cell differentiation and insulin production (12,13), whereas its role in the brain remains incomplete. Nevertheless, miR-7 expression seems to be highly regulated in the brain by several other posttranscriptional regulators, such as RNA binding proteins (RBPs) (14) and miRNA sponges (15), suggesting its important role in the CNS.…”

Enteroendocrine Progenitor Cell–Enriched miR-7 Regulates Intestinal Epithelial Proliferation in an Xiap-Dependent Manner

“…Notably, class C miRNAs include miR-7b, which has been previously extensively studied in the context of endocrine pancreatic development and function. [8][9][10][11][12][13][14][15] MiR-7 was also shown to be enriched in a specific subtype of mature EECs and cholecystokininproducing EECs, 16 and also in enterochromaffin cellderived tumors 17 ; however, importantly, the expression pattern of miR-7 (or any other miRNA) across the entire EEC lineage trajectory has never before been reported.…”

The Landscape of microRNAs in βCell: Between Phenotype Maintenance and Protection

“…Of relevance, miR-7 is also differentially expressed in hIPSCs [ 63 ] and in human embryonic stem cells (hESCs) during differentiation toward β cell fate [ 67 ]. Importantly, induced overexpression of miR-7 during hESCs differentiation improved generation of mature pancreatic insulin-producing cells and revealed the critical role of miR-7 in the modulation of β cell differentiation.…”