Quantitative analysis of redox proteome reveals oxidation-sensitive protein thiols acting in fundamental processes of developmental hematopoiesis

K Pimkova, M Jassinskaja, R Munita, M Ciesla, N Guzzi, P Cao Thi Ngoc, M Vajrychova, E Johansson, C Bellodi, Jenny Hansson

Research output: Contribution to journalArticlepeer-review

Abstract

Fetal and adult hematopoietic stem and progenitor cells (HSPCs) are characterized by distinct redox homeostasis that may influence their differential cellular behavior in normal and malignant hematopoiesis. In this work, we have applied a quantitative mass spectrometry-based redox proteomic approach to comprehensively describe reversible cysteine modifications in primary mouse fetal and adult HSPCs. We defined the redox state of 4,438 cysteines in fetal and adult HSPCs and demonstrated a higher susceptibility to oxidation of protein thiols in fetal HSPCs. Our data identified ontogenic changes to oxidation state of thiols in proteins with a pronounced role in metabolism and protein homeostasis. Additional redox proteomic analysis identified oxidation changes to thiols acting in mitochondrial respiration as well as protein homeostasis to be triggered during onset of MLL-ENL leukemogenesis in fetal HSPCs. Our data has demonstrated that redox signaling contributes to the regulation of fundamental processes of developmental hematopoiesis and has pinpointed potential targetable redox-sensitive proteins in in utero-initiated MLL-rearranged leukemia.

Original languageEnglish
Article number102343
JournalRedox Biology
Volume53
DOIs
Publication statusPublished - 2022 Jul

Bibliographical note

Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

Subject classification (UKÄ)

  • Cell Biology
  • Medical Genetics

Free keywords

  • Animals
  • Cysteine/metabolism
  • Hematopoiesis
  • Mice
  • Oxidation-Reduction
  • Proteome/metabolism
  • Proteomics
  • Sulfhydryl Compounds

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