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 gly...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 embryonic 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 cancer cells.Altogether,this study provides insights into the potential function and underlying mechanism of acidic pH in pluripotent stem cells(PSCs).展开更多
基金This work was supported by the National Key Research and Development Program of China(2016YFA0100701 and 2018YFA0107601)the National Natural Science Foundation of China(91640116,91940302,31622033,and 31821091)the Fundamental Research Funds for the Central Universities(3332018008).
文摘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 embryonic 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 cancer cells.Altogether,this study provides insights into the potential function and underlying mechanism of acidic pH in pluripotent stem cells(PSCs).
