The role of m6A mRNA modification in normal and malignant hematopoiesis

生物 造血 祖细胞 细胞生物学 骨髓 干细胞 免疫学 造血干细胞 癌症研究
作者
Zhangjing Ma,Ryohichi Sugimura,Kathy O. Lui
出处
期刊:Journal of Leukocyte Biology [Wiley]
卷期号:115 (1): 100-115
标识
DOI:10.1093/jleuko/qiad061
摘要

Abstract Hematopoiesis is a highly orchestrated biological process sustaining the supply of leukocytes involved in the maintenance of immunity, O2 and CO2 exchange, and wound healing throughout the lifetime of an animal, including humans. During early hematopoietic cell development, several waves of hematopoiesis require the precise regulation of hematopoietic ontogeny as well as the maintenance of hematopoietic stem and progenitor cells in the hematopoietic tissues, such as the fetal liver and bone marrow. Recently, emerging evidence has suggested the critical role of m6A messenger RNA (mRNA) modification, an epigenetic modification dynamically regulated by its effector proteins, in the generation and maintenance of hematopoietic cells during embryogenesis. In the adulthood, m6A has also been demonstrated to be involved in the functional maintenance of hematopoietic stem and progenitor cells in the bone marrow and umbilical cord blood, as well as the progression of malignant hematopoiesis. In this review, we focus on recent progress in identifying the biological functions of m6A mRNA modification, its regulators, and downstream gene targets during normal and pathological hematopoiesis. We propose that targeting m6A mRNA modification could offer novel insights into therapeutic development against abnormal and malignant hematopoietic cell development in the future.
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