Quantitative analysis of redox proteome reveals protein thiol switches regulating fundamental processes in developmental haematopoiesis

ABSTRACT: Foetal and adult hematopoietic stem and progenitor cells (HSPCs) are characterized by distinct redox homeostasis that may influence their differential cellular behaviour in normal and malignant haematopoiesis. In this work, we have applied a quantitative mass spectrometry-based redox proteomic approach to comprehensively describe reversible cysteine modifications in primary mouse foetal and adult HSPCs. We defined the redox state of 4455 cysteines in foetal and adult HSPCs and demonstrated a higher susceptibility to oxidation of protein thiols in foetal HSPCs. Our data identified ontogenically active redox switches in proteins with a pronounced role in metabolism and protein homeostasis. Additional redox proteomic analysis identified redox switches acting in mitochondrial respiration as well as protein homeostasis to be triggered during onset of MLL-ENL leukemogenesis in foetal HSPCs. Our data has demonstrated that redox signalling contributes to the regulation of fundamental processes of developmental haematopoiesis and has pinpointed potential targetable redox-sensitive proteins in in utero-initiated MLL-rearranged leukaemia.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver, Stem Cell, Embryonic Stem Cell, Bone Marrow

DISEASE(S): Acute Leukemia

SUBMITTER: Kristyna Pimkova  

LAB HEAD: Kristyna Pimkova

PROVIDER: PXD030043 | Pride | 2022-06-09

REPOSITORIES: Pride