Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells

作者全名："Yang, Bijie; Liu, Yuanyuan; Xiao, Feifei; Liu, Zhilong; Chen, Zhe; Li, Zhigang; Zhou, Chengfang; Kuang, Mei; Shu, Yi; Liu, Shan; Zou, Lin"

作者地址："[Yang, Bijie; Shu, Yi; Liu, Shan; Zou, Lin] Chongqing Med Univ, Key Lab Child Dev & Disorders, Chongqing Engn Res Ctr Stem Cell Therapy, Ctr Clin Mol Med & Newborn Screening,Childrens Hos, 136 Zhongshan Er Rd, Chongqing 400014, Peoples R China; [Zou, Lin] Chongqing Engn Res Ctr Stem Cell Therapy, Chongqing, Peoples R China; [Liu, Yuanyuan; Chen, Zhe; Li, Zhigang; Zhou, Chengfang] Chongqing Med Univ, Inst Life Sci, Chongqing, Peoples R China; [Xiao, Feifei; Liu, Zhilong; Kuang, Mei] Third Mil Med Univ, Army Med Univ, Southwest Hosp, Dept Hematol, Chongqing, Peoples R China"

通信作者："Zou, L (通讯作者)，Chongqing Med Univ, Key Lab Child Dev & Disorders, Chongqing Engn Res Ctr Stem Cell Therapy, Ctr Clin Mol Med & Newborn Screening,Childrens Hos, 136 Zhongshan Er Rd, Chongqing 400014, Peoples R China.; Zou, L (通讯作者)，Chongqing Engn Res Ctr Stem Cell Therapy, Chongqing, Peoples R China."

来源：OPEN MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001044951200001

JCR分区：Q2

影响因子：1.7

年份：2023

卷号：18

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：hematopoietic stem cells; self-renewal; demethylation

摘要："Alkbh5 is one of the primary demethylases responsible for reversing N6-methyladenosine (m(6)A) modifications on mRNAs, and it plays a crucial role in many physiological and pathological processes. Previous studies have shown that Alkbh5 is required for maintaining the function of leukemia stem cells but is dispensable for normal hematopoiesis. In this study, we found that Alkbh5 deletion led to a moderate increase in the number of multiple progenitor cell populations while compromising the long-term self-renewal capacity of hematopoietic stem cells (HSCs). Here, we used RNA-seq and m(6)A-seq strategies to explore the underlying molecular mechanism. At the molecular level, Alkbh5 may regulate hematopoiesis by reducing m(6)Amodification of Cebpa andmaintaining gene expression levels. Overall, our study unveiled an essential role for Alkbh5 in regulating HSC homeostasis and provides a reference for future research in this area."

基金机构："Natural Science Foundation of China [81870126, 82070167, 82100131]; Chongqing Municipal Social People's Livelihood Technology Innovation Project [cstc2019jscx-msxm0189]"

基金资助正文："This research was supported by grants from the Natural Science Foundation of China (grant nos 81870126, 82070167, and 82100131) and the Chongqing Municipal Social People's Livelihood Technology Innovation Project (cstc2019jscx-msxm0189)."