Comprehensive proteomic description of ontogenic changes in hematopoietic stem and progenitor cells

Abstract

Hematopoiesis in the fetus and adult is characterized by distinct features that reflect the vastly different needs of the organism during different stages of ontogeny. Although the functional differences between fetal and adult hematopoietic stem and progenitor cells (HSPCs) are well-established, the molecular programs that govern these differences remain elusive. In this study, we have utilized an in-depth mass spectrometry-based quantitative proteomics approach to compare the full proteomes of ex vivo isolated and FACS-sorted mouse fetal liver and adult bone marrow HSPCs. Close to 7000 proteins were identified, allowing us to comprehensively describe the proteomic differences between these cells. 454 proteins showed differential expression, indicative of the divergent nature of fetal and adult hematopoiesis. While the proteome of fetal HSPCs is fairly simple, with main features being cell cycle and cell proliferation, their adult counterpart has a more advanced proteome, including an arsenal of proteins important for viral and bacterial defense, as well as protection against ROS-induced protein oxidation. Our further analyses of Type I interferon signaling showed that fetal HSPCs are sensitive to Interferon alpha (IFNa) in vitro, although their exposure and response to IFNa in their native environment is mild. Our results provide new and important insights into the molecular landscape of fetal and adult hematopoiesis that advance our understanding of normal and malignant hematopoiesis during fetal and adult life.