Systematic metabolome analysis of hematopoietic cells identified uridine as a vital anti-aging factor in hematopoiesis

In this study, we employed immunomagnetic enrichment and fluorescence-activated cell sorting (FACS) to isolate 15 hematopoietic cell types, over 9×108 hematopoietic cells from 200 young and 150 aged mice, ranging from HSPCs to mature blood cells. UPLC-MS/MS untargeted analysis identified about 2000 metabolites in each cell population, which contributed to define cell-specific signatures and depict aging landscape of blood cells. We further validated our findings by experimentally screening metabolites delaying senescence and identified uridine as potential regulator to rejuvenate aged HSPCs. To enable public access to our dataset, we have constructed an open-source platform (MetaB, www.XXX.com) for easy data browsing and analysis. Collectively, our study developed a solid reference benchmark for metabolic studies in hematopoietic system and provided additional clarity to the mechanisms underlying hematopoietic aging. Overall design: Comparative gene expression profiling analysis of RNA-seq data for uncultured aged HSPCs, uncultured young HSPCs, aged HSPCs cultured with vehicle and aged HSPCs cultured with uridine.