College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, 030801, China; Senior Department of Hematology, the Fifth Medical Center of PLA General Hospital, Beijing, 100071, China.
Senior Department of Hematology, the Fifth Medical Center of PLA General Hospital, Beijing, 100071, China; Medical School of the Chinese PLA General Hospital, Beijing, 100039, China.
Biochem Biophys Res Commun. 2024 Nov 19;734:150661. doi: 10.1016/j.bbrc.2024.150661. Epub 2024 Sep 4.
Hematopoietic stem progenitor cells (HSPCs) give rise to the hematopoietic system, maintain hematopoiesis throughout the lifespan, and undergo molecular and functional changes during their development and aging. The importance of hematopoietic stem cell (HSC) biology has led to their extensive characterization at genomic and transcriptomic levels. However, the proteomics of HSPCs throughout the murine lifetime still needs to be fully completed. Here, using mass spectrometry (MS)-based quantitative proteomics, we report on the dynamic changes in the proteome of HSPCs from four developmental stages in the fetal liver (FL) and the bone marrow (BM), including E14.5, young (2 months), middle-aged (8 months), and aging (18 months) stages. Proteomics unveils highly dynamic protein kinetics during the development and aging of HSPCs. Our data identify stage-specific developmental features of HSPCs, which can be linked to their functional maturation and senescence. Our proteomic data demonstrated that FL HSPCs depend on aerobic respiration to meet their proliferation and oxygen supply demand, while adult HSPCs prefer glycolysis to preserve the HSC pool. By functional assays, we validated the decreased mitochondrial metabolism, glucose uptake, reactive oxygen species (ROS) production, protein synthesis rate, and increased glutathione S-transferase (GST) activity during HSPC development from fetal to adult. Distinct metabolism pathways and immune-related pathways enriched in different HSPC developmental stages were revealed at the protein level. Our study will have broader implications for understanding the mechanism of stem cell maintenance and fate determination and reversing the HSC aging process.
造血干祖细胞 (HSPC) 产生造血系统，在整个生命周期内维持造血，并在其发育和衰老过程中发生分子和功能变化。造血干细胞 (HSC) 生物学的重要性导致了它们在基因组和转录组水平上的广泛表征。然而，整个鼠寿命的 HSPC 蛋白质组学仍需要完全完成。在这里，我们使用基于质谱 (MS) 的定量蛋白质组学，报告了来自胎肝 (FL) 和骨髓 (BM) 四个发育阶段的 HSPC 蛋白质组的动态变化，包括 E14.5、幼龄 (2 个月)、中年 (8 个月) 和老年 (18 个月) 阶段。蛋白质组学揭示了 HSPC 发育和衰老过程中高度动态的蛋白质动力学。我们的数据确定了 HSPC 的特定于阶段的发育特征，这些特征可以与其功能成熟和衰老相关联。我们的蛋白质组学数据表明，FL HSPC 依赖有氧呼吸来满足其增殖和氧气供应需求，而成年 HSPC 更喜欢糖酵解来维持 HSC 池。通过功能测定，我们验证了从胎儿到成年 HSPC 发育过程中，线粒体代谢、葡萄糖摄取、活性氧 (ROS) 产生、蛋白质合成率和谷胱甘肽 S-转移酶 (GST) 活性降低。在蛋白质水平上揭示了不同 HSPC 发育阶段中富集的不同代谢途径和免疫相关途径。我们的研究将对理解干细胞维持和命运决定的机制以及逆转 HSC 衰老过程具有更广泛的意义。
