ALKBH3 is dispensable in maintaining hematopoietic stem cells but forced ALKBH3 rectified the differentiation skewing of aged hematopoietic stem cells  

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作  者:Hanqing He Yuqian Wang Jianwei Wang 

机构地区:[1]School of Pharmaceutical Sciences,Tsinghua University,Beijing 100084,China [2]Beijing Advanced Innovation Center for Structural Biology,Tsinghua University,Beijing 100084,China

出  处:《Blood Science》2020年第4期137-143,共7页血液科学(英文)

基  金:This work was supported by grant numbers 2018YFA0800200,2017YFA0104000,Z181100001818005 and 91849106 to J.W;W.,from the National KeyR&D Program of China or the Beijing Municipal Science&Technology Commission and the National Natural Science Foundation of China.

摘  要:ALKBH3,a demethylase responsible for demethylating N1-methyladenosine(m^(1)A)in mRNA and N1-methyldeoxyadenosine in single-stranded DNA,plays an important role in DNA repair and cancer cell proliferation.However,its function in hematopoietic stem cells(HSCs)is unknown.In this study,we generated Alkbh3 knockout mice and observed that the deletion of Alkbh3 does not impair the reconstitution capacity of HSCs in both primary and secondary transplantation.Aged hematopoietic stem and progenitor cells exhibit increased expression of ALKBH3.Forced ALKBH3 rescued the differentiation skewing without affecting the reconstitution capacity of aged HSCs.In brief,our study for the first time investigated the functional role of ALKBH3 in hematopoietic system,and observed that ALKBH3 is dispensable for HSCs maintenance and differentiation,but overexpression of ALKBH3 rectified the differentiation skewing of aged HSCs.

关 键 词:AGING ALKBH3 Hematopoietic stem cell 

分 类 号:R57[医药卫生—消化系统]

 

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