Glycogen accumulation, central carbon metabolism, and aging of hematopoietic stem and progenitor cells
Glycogen accumulation, central carbon metabolism, and aging of hematopoietic stem and progenitor cells
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糖原积累、中心碳代谢以及造血干细胞和祖细胞的衰老
DOI：
10.1038/s41598-020-68396-2
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发表时间：
2020
影响因子：
4.6
通讯作者：
Ho Anthony D.
中科院分区：
文献类型：
--
作者：
Poisa-Beiro Laura;Thoma Judith;Landry Jonathan;Sauer Sven;Yamamoto Akihisa;Eckstein Volker;Romanov Natalie;Raffel Simon;Hoffmann Georg F.;Bork Peer;Benes Vladimir;Gavin Anne-Claude;Tanaka Motomu;Ho Anthony D.
最近的蛋白质组学数据显示衰老的人类造血干细胞和祖细胞（HPC、CD34+细胞）碳和糖原代谢上调，受此启发，本报告探讨了这是由每个细胞的 HPC 糖酵解升高引起的，还是由糖酵解程度更高的亚群引起的。与年轻受试者（<35 岁）相比，老年受试者（>50 岁）个体 CD34+ 细胞中的平均糖原含量高出 3.5 倍，且异质性更强。 HPC 中代表性的糖酵解酶活性证实了老年受试者的糖酵解显着增加。来自老年受试者的 HPC 可分为三个不同的子集，分别具有高、中和低葡萄糖摄取 (GU) 能力，而具有高 GU 能力的子集在年轻受试者中几乎检测不到。因此，我们得出结论，衰老 HPC 中糖酵解的上调是由糖酵解性更强的 HPC 亚群的扩张引起的。由于单细胞 RNA 分析还证明该亚群与骨髓分化和增殖增加有关，因此可以利用该亚群的分离和机制表征来阐明治疗干预的具体目标，以恢复老化 HPC 的谱系平衡。
Inspired by recent proteomic data demonstrating the upregulation of carbon and glycogen metabolism in aging human hematopoietic stem and progenitor cells (HPCs, CD34+ cells), this report addresses whether this is caused by elevated glycolysis of the HPCs on a per cell basis, or by a subpopulation that has become more glycolytic. The average glycogen content in individual CD34+ cells from older subjects (> 50 years) was 3.5 times higher and more heterogeneous compared to younger subjects (< 35 years). Representative glycolytic enzyme activities in HPCs confirmed a significant increase in glycolysis in older subjects. The HPCs from older subjects can be fractionated into three distinct subsets with high, intermediate, and low glucose uptake (GU) capacity, while the subset with a high GU capacity could scarcely be detected in younger subjects. Thus, we conclude that upregulated glycolysis in aging HPCs is caused by the expansion of a more glycolytic HPC subset. Since single-cell RNA analysis has also demonstrated that this subpopulation is linked to myeloid differentiation and increased proliferation, isolation and mechanistic characterization of this subpopulation can be utilized to elucidate specific targets for therapeutic interventions to restore the lineage balance of aging HPCs.