Mettl3-Mettl14 methyltransferase complex regulates the quiescence of adult hematopoietic stem cells
Dear Editor,N6-methyladenosine (m6A) is a common modification of mRNA that is catalyzed by the Mettl3-Mettl14 methyltransferase complex1,with WTAP as its regulatory subunit2.The physiological importance of m6A has been evidenced by its pivotal roles in tissue development and differentiation3-9.Hematopoietic stem cells (HSCs) are self-renewable multipotent progenitor cells that sustain all blood cell lineages throughout life.It has been well recognized that epigenetic modifications,such as histone or DNA modifications,are implicated in HSC self-renewal10.Recent studies have shown that the mRNA modification m6A also functions in the hematopoietic system.In human,Mettl3-Mettl14-mediated m6A was found to promote the development of acute myeloid leukemia and maintain leukemia-initiating cells5,6,11.In zebrafish and mouse,knockdown of Mettl3 blocked the endothelial-to-hematopoietic transition during embryonic development,thereby repressing the generation of the earliest HSCs7.Surprisingly,deletion of Mettl3 in Vav1-cre;Mettl3fl/fl mouse embryos did not have a significant effect on the number or function of E10.5 fetal hematopoietic stem and progenitor cells (HSPCs)4,suggesting that cell-autonomous m6A is dispensable for HSC self-renewal during early development.Conditional deletion of Mett/14 in adult mice caused a mild but significant reduction of the hematopoietic repopulation ability in recipient mice6.The repopulation defect observed in Mettl14-deficient bone marrow cells could be interpreted as a myeloid differentiation defect or a defect in HSC self-renewal.However,until now,there is a lack of evidence that m6A plays a role in HSC self-renewal in the bone marrow.In this study,we took genetic approaches to investigate the physiological roles of Mettl3 and Mettl14 in the regulation of HSC self-renewal in adult mouse bone marrow.
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the Strategic Priority Research Program of the Chinese Academy of SciencesXDA16020202;the National Key Program on Stem Cell and Translational Research2018YFA0107201;the National Natural Science Foundation of China31771637,81730006,81570093
2018-10-22（万方平台首次上网日期，不代表论文的发表时间）
共3页
952-954
