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A network of microRNAs acts to promote cell cycle exit and differentiation of human pancreatic endocrine cells

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Item Type:Article
Title:A network of microRNAs acts to promote cell cycle exit and differentiation of human pancreatic endocrine cells
Creators Name:Jin, W. and Mulas, F. and Gaertner, B. and Sui, Y. and Wang, J. and Matta, I. and Zeng, C. and Vinckier, N. and Wang, A. and Nguyen-Ngoc, K.V. and Chiou, J. and Kaestner, K.H. and Frazer, K.A. and Carrano, A.C. and Shih, H.P. and Sander, M.
Abstract:Pancreatic endocrine cell differentiation is orchestrated by the action of transcription factors that operate in a gene regulatory network to activate endocrine lineage genes and repress lineage-inappropriate genes. MicroRNAs (miRNAs) are important modulators of gene expression, yet their role in endocrine cell differentiation has not been systematically explored. Here we characterize miRNA-regulatory networks active in human endocrine cell differentiation by combining small RNA sequencing, miRNA over-expression, and network modeling approaches. Our analysis identified Let-7g, Let-7a, miR-200a, miR-127, and miR-375 as endocrine-enriched miRNAs that drive endocrine cell differentiation-associated gene expression changes. These miRNAs are predicted to target different transcription factors, which converge on genes involved in cell cycle regulation. When expressed in human embryonic stem cell-derived pancreatic progenitors, these miRNAs induce cell cycle exit and promote endocrine cell differentiation. Our study delineates the role of miRNAs in human endocrine cell differentiation and identifies miRNAs that could facilitate endocrine cell reprogramming.
Keywords:Molecular Mechanism of Gene Regulation, Molecular Network, Endocrinology, Stem Cells Research
Publisher:Cell Press
Page Range:681-694
Date:22 November 2019
Official Publication:https://doi.org/10.1016/j.isci.2019.10.063
PubMed:View item in PubMed

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