Foetal and adult HSPCs - Comprehensive Proteomic Characterization of Ontogenic Changes in Hematopoietic Stem and Progenitor Cells

ABSTRACT: Haematopoietic stem and progenitor cells (HSPCs) in the foetus and adult possess distinct molecular landscapes that regulate cell fate and change their susceptibility to initiation and progression of haematopoietic malignancies. The proteomic programs that govern these differences remain elusive. In this study, we have utilized a mass spectrometry-based quantitative proteomics approach to comprehensively describe and compare the proteome of foetal and adult HSPCs. We found that the proteome of foetal HSPCs is relatively simple, characterized by proteins involved in cell cycle and cell proliferation, while their adult counterparts are defined by a larger set of proteins that are involved in more diverse cellular processes. These adult characteristics include an arsenal of proteins important for viral and bacterial defence, as well as protection against ROS-induced protein oxidation. Our further analyses of Type I interferon signalling shows that foetal HSPCs are sensitive to Interferon a (IFNa), which impairs their production of mature lymphoid cells, whereas stimulation with IFNa to the pregnant mother enhances the production of early progenitors from foetal HSCs. Our results provide new and important insights into the molecular landscape of foetal and adult haematopoiesis that advance our understanding of normal and malignant haematopoiesis during foetal and adult life.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver, Kit And Sca1-positive Hematopoietic Stem Cell, Bone Marrow

SUBMITTER: Jenny Hansson  

LAB HEAD: Jenny Hansson

PROVIDER: PXD006876 | Pride | 2017-12-12

REPOSITORIES: Pride