miR-375通过在不同阶段影响不同靶基因来促进胰腺分化。

miR-375 Promotes Pancreatic Differentiation by Affecting Different Target Genes at Different Stages.

作者信息

Lu Zhenyu, Wang Jing, Wang Xu, Li Zhiying, Niu Dan, Wang Min, Xiang Jinzhu, Yue Yongli, Xia Yajuan, Li Xueling

机构信息

State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot, China.

Inner Mongolia Center for Disease Control and Prevention, Hohhot, China.

出版信息

Stem Cells Int. 2021 Apr 7;2021:6642983. doi: 10.1155/2021/6642983. eCollection 2021.

DOI:10.1155/2021/6642983

PMID:33897780

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8052179/

Abstract

Human embryonic stem cells (hESCs) possess the ability to differentiate into insulin-producing cells (IPCs), which can be used to treat type I diabetes. miR-375 is an essential transcriptional regulator in the development and maturation of the pancreas. In this study, we optimized a protocol to differentiate hESCs into IPCs and successfully obtained IPCs. Then, we performed overexpression and inhibition experiments of miR-375 on cells at different stages of differentiation and performed RNA-seq. The results showed that the expression of miR-375 fluctuated during hESC differentiation and was affected by miR-375 mimics and inhibitors. miR-375 influences global gene expression and the target genes of miR-375. The overexpression of miR-375 can cause changes in multiple signaling pathways during pancreatic development. miR-375 is a major participant in the differentiation of pancreatic -cells through different target genes at different stages. This study provides new ideas for further investigation of how microRNAs affect cell fate and gene transcription.

摘要

人类胚胎干细胞（hESCs）具有分化为胰岛素产生细胞（IPCs）的能力，这些细胞可用于治疗I型糖尿病。miR-375是胰腺发育和成熟过程中的一种重要转录调节因子。在本研究中，我们优化了一种将hESCs分化为IPCs的方案，并成功获得了IPCs。然后，我们在分化的不同阶段对细胞进行了miR-375的过表达和抑制实验，并进行了RNA测序。结果表明，miR-375在hESC分化过程中的表达波动，且受到miR-375模拟物和抑制剂的影响。miR-375影响全局基因表达以及miR-375的靶基因。miR-375的过表达可导致胰腺发育过程中多个信号通路发生变化。miR-375通过不同阶段的不同靶基因成为胰腺β细胞分化的主要参与者。本研究为进一步研究微小RNA如何影响细胞命运和基因转录提供了新的思路。