Xue Jianqi, Du Ruikai, Ling Shukuan, Song Jinping, Yuan Xinxin, Liu Caizhi, Sun Weijia, Li Yuheng, Zhong Guohui, Wang Yinbo, Yuan Guodong, Jin Xiaoyan, Liu Zizhong, Zhao Dingsheng, Li Youyou, Xing Wenjuan, Fan Yuanyuan, Liu Zifan, Pan Junjie, Zhen Zhen, Zhao Yunzhang, Yang Qinna, Li Jianwei, Chang Yan-Zhong, Li Yingxian
Laboratory of Molecular Iron Metabolism, Key Laboratory of Molecular and Cellular Biology of Ministry of Education, College of Life Science, Hebei Normal University, Shijiazhuang, China.
State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China.
Front Bioeng Biotechnol. 2022 Apr 21;10:850303. doi: 10.3389/fbioe.2022.850303. eCollection 2022.
As hematopoietic stem cells can differentiate into all hematopoietic lineages, mitigating the damage to hematopoietic stem cells is important for recovery from overdose radiation injury. Cells in bone marrow microenvironment are essential for hematopoietic stem cells maintenance and protection, and many of the paracrine mediators have been discovered in shaping hematopoietic function. Several recent reports support exosomes as effective regulators of hematopoietic stem cells, but the role of osteoblast derived exosomes in hematopoietic stem cells protection is less understood. Here, we investigated that osteoblast derived exosomes could alleviate radiation damage to hematopoietic stem cells. We show that intravenous injection of osteoblast derived exosomes promoted WBC, lymphocyte, monocyte and hematopoietic stem cells recovery after irradiation significantly. By sequencing osteoblast derived exosomes derived miRNAs and verified , we identified miR-21 is involved in hematopoietic stem cells protection via targeting PDCD4. Collectively, our data demonstrate that osteoblast derived exosomes derived miR-21 is a resultful regulator to radio-protection of hematopoietic stem cells and provide a new strategy for reducing radiation induced hematopoietic injury.
由于造血干细胞可分化为所有造血谱系,减轻对造血干细胞的损伤对于从过量辐射损伤中恢复至关重要。骨髓微环境中的细胞对于造血干细胞的维持和保护至关重要,并且已经发现许多旁分泌介质在塑造造血功能方面发挥作用。最近的几份报告支持外泌体作为造血干细胞的有效调节剂,但成骨细胞衍生的外泌体在造血干细胞保护中的作用尚不清楚。在这里,我们研究了成骨细胞衍生的外泌体是否可以减轻对造血干细胞的辐射损伤。我们发现静脉注射成骨细胞衍生的外泌体可显著促进照射后白细胞、淋巴细胞、单核细胞和造血干细胞的恢复。通过对成骨细胞衍生的外泌体来源的miRNA进行测序并验证,我们确定miR-21通过靶向PDCD4参与造血干细胞的保护。总的来说,我们的数据表明成骨细胞衍生的外泌体来源的miR-21是造血干细胞放射防护的有效调节剂,并为减少辐射诱导的造血损伤提供了新策略。