Acidic pH transiently prevents the silencing of self-renewal and dampens microRNA function in embryonic stem cells

• 作者: Wenting Guo Shaohua Wang Xiaoshan Zhang Ming Shi Feifei Duan Jing Hao Kaili Gu Li Quan Yixia Wu Zhiyong Liang Yangming Wang
• 来源期刊: 科学通报（英文版）
• 年，卷（期）: 2021,（13）
• 所属期刊栏目: ARTICLES
• 页码范围: 1319-1329
• 页数: 11页
• 语种: 英文

摘要

Enhanced glycolysis is a distinct feature associated with numerous stem cells and cancer cells.However,little is known about its regulatory roles in gene expression and cell fate determination.Here,we confirm that glycolytic metabolism and lactate production decrease during the differentiation of mouse embry-onic stem cells(mESCs).Importantly,acidic pH due to lactate accumulation can transiently prevent the silencing of mESC self-renewal in differentiation conditions.Furthermore,acidic pH partially blocks the differentiation of human ESCs(hESCs).Mechanistically,acidic pH downregulates AGO1 protein and de-represses a subset of mRNA targets of miR-290/302 family of microRNAs which facilitate the exit of naive pluripotency state in mESCs.Interestingly,AGO1 protein is also downregulated by acidic pH in can-cer cells.Altogether,this study provides insights into the potential function and underlying mechanism of acidic pH in pluripotent stem cells(PSCs).