Comprehensive Proteomic Characterization of Ontogenic Changes in Hematopoietic Stem and Progenitor Cells

Hematopoietic stem and progenitor cells (HSPCs) in the fetus and adult possess distinct molecular landscapes that regulate cell fate and change their susceptibility to initiation and progression of hematopoietic malignancies. Here, we applied in-depth quantitative proteomics to comprehensively describe and compare the proteome of fetal and adult HSPCs. Our data uncover a striking difference in complexity of the cellular proteomes, with more diverse adult-specific HSPC proteomic signatures. The differential protein content in fetal and adult HSPCs indicate distinct metabolic profiles and protein complex stoichiometries. Additionally, adult characteristics include an arsenal of proteins linked to viral and bacterial defense, as well as protection against ROS-induced protein oxidation. Further analyses show that interferon α as well as Neutrophil elastase, has distinct functional effects in fetal and adult HSPCs. This study provides a rich resource aimed toward an enhanced mechanistic understanding of normal and malignant hematopoiesis during fetal and adult life. Jassinskaja et al. describe the proteomic makeup of fetal and adult hematopoietic stem and progenitor cells. They uncover differences in protein complex stoichiometry, defense against pathogens and ROS, and show that IFN-α has distinct functional effects on fetal and adult HSPCs.