MicroRNA 34a promotes ionizing radiation–induced DNA damage repair in murine hematopoietic stem cells

Abstract

Hematopoietic stem cells (HSCs) establish the entire hematopoietic system and maintain lifelong hematopoiesis. Previous studies have reported the significance of microRNAs (miRNAs) in the regulation of self-renewal and differentiation of HSCs. In this study, we show that the expression of miRNA 34a (miR-34a) is markedly up-regulated in HSCs from mice subjected to ionizing radiation (IR). Reduced numbers and DNA damage repair, as well as increased apoptosis, are observed in HSCs from miR-34a-deficient mice induced by irradiation, although miR-34a is dispensable for steady-state hematopoiesis. Further investigations show that HSCs deficient in miR-34a exhibit decreased expressions of DNA repair-associated genes involved in homologous recombination and nonhomologous end joining. Competitive transplantation confirms that loss of miR-34a leads to more severe impairment of the long-term hematopoietic function of HSCs after irradiation exposure. Consistently, treating mice with an miR-34a agomir can significantly alleviate irradiation-induced DNA damage in HSCs. Our findings demonstrate that miR-34a contributes to promoting HSCs' survival after irradiation, which provides a promising approach for protecting HSCs from IR.-Zeng, H., Hu, M., Lu, Y., Zhang, Z., Xu, Y., Wang, S., Chen, M., Shen, M., Wang, C., Chen, F., Du, C., Tang, Y., Su,Y., Chen, S., Wang, J. MicroRNA 34a promotes ionizing radiation-induced DNA damage repair in murine hematopoietic stem cells.