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Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells. 2023

Bijie Yang, and Yuanyuan Liu, and Feifei Xiao, and Zhilong Liu, and Zhe Chen, and Zhigang Li, and Chengfang Zhou, and Mei Kuang, and Yi Shu, and Shan Liu, and Lin Zou
Center for Clinical Molecular Medicine & Newborn Screening, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Engineering Research Center of Stem Cell Therapy, 400014, Chongqing, PR China.

Alkbh5 is one of the primary demethylases responsible for reversing N6-methyladenosine (m6A) 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 m6A-seq strategies to explore the underlying molecular mechanism. At the molecular level, Alkbh5 may regulate hematopoiesis by reducing m6A modification of Cebpa and maintaining 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.

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