Deciphering the Heterogeneity of Mitochondrial Functions During Hematopoietic Lineage Differentiation
Deciphering the Heterogeneity of Mitochondrial Functions During Hematopoietic Lineage Differentiation
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破译造血谱系分化过程中线粒体功能的异质性
DOI：
10.1007/s12015-022-10354-8
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发表时间：
2022-02-21
影响因子：
4.8
通讯作者：
Ru, Yongxin
中科院分区：
文献类型：
--
作者：
Liang, Haoyue;Dong, Shuxu;Ru, Yongxin
背景线粒体功能的异质性是造血细胞分化的一个重要特征，但其阶段性贡献尚未得到充分研究。为了建立比较造血干细胞(HSCs)、造血祖细胞(HPC)和已分化血细胞的谱系分化的模型，分析了线粒体质量(MM)、线粒体膜电位(MMP)、活性氧(ROS)和有丝分裂水平。结果与讨论HSCs的线粒体代谢活性低于承诺的祖细胞群体，表现为较低的MM、MMPs和ROS和较高的有丝分裂能力。在线粒体数量和功能方面，HPC1比HPC2具有更多的干细胞特征和承诺的祖细胞群体。成熟血细胞线粒体代谢的异质性大于造血干/祖细胞，粒细胞与单核细胞相似。此外，HSCs在选择与有丝分裂相关的PINK1/PARK2、BNIP3/Nix和Fundc1通路时表现出异质性。髓系分化比淋巴系分化具有更大的造血细胞形态和功能异质性。此外，与正常造血细胞相比，白血病干细胞具有更高的有氧代谢和更好的干细胞功能。结论本研究为系统研究不同类型造血细胞在生理和病理条件下线粒体代谢功能提供了一套完整的方法和基础参考值。这些发现为未来基于线粒体代谢的肿瘤和衰老的研究提供了参考。
BackgroundThe heterogeneity of mitochondrial function is an important feature of hematopoietic cell lineage differentiation, but its stage wise contribution is not adequately studied. To establish a model to compare the lineage differentiation of hematopoietic stem cells (HSCs), hematopoietic progenitor cells (HPCs), and differentiated blood cells, the mitochondrial mass (MM), mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and mitophagy level were analyzed.Results and DiscussionHSCs had lower mitochondrial metabolic activity than committed progenitor populations, indicated by lower MM, MMP, and ROS and higher mitophagy. HPC1s shared more stem cell characteristics than HPC2s and committed progenitor populations in terms of mitochondrial number and function. The mitochondrial metabolism of mature blood cells had greater heterogeneity than hematopoietic stem and progenitor cells, with granulocytes being similar to monocytes. Moreover, HSCs exhibited heterogeneity in the selection of mitophagy-related PINK1/PARK2, BNIP3/NIX, and FUNDC1 pathways. Myeloid differentiation had greater morphological and functional heterogeneity of hematopoietic cells than lymphoid differentiation. Additionally, leukemia stem cells had higher aerobic metabolism and better stem cell function through elevated mitophagy than normal hematopoietic cells. ROS and MMP levels in differentiated leukemia cells were higher, but the level of mitophagy was lower than in differentiated hematopoietic cells.ConclusionThis study provides a complete set of methods and basic reference values for the systematic study of the mitochondrial metabolic function of different types of hematopoietic cells under physiological and pathological conditions. The findings contribute to the future research of tumor and aging based on mitochondrial metabolism.Graphical abstract