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

• Published in: Redox biology Vol. 53; p. 102343
• Main Authors: Pimkova, K., Jassinskaja, M., Munita, R., Ciesla, M., Guzzi, N., Cao Thi Ngoc, P., Vajrychova, M., Johansson, E., Bellodi, C., Hansson, J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2022; Elsevier
• Subjects: Animals; Basic Medicine; Biologi; Biological Sciences; Cell Biology; Cellbiologi; Cysteine oxidative modifications; Cysteine/metabolism; Developmental biology; Hematopoiesis; Leukemia; Medical and Health Sciences; Medical Genetics; Medicin och hälsovetenskap; Medicinsk genetik; Medicinska och farmaceutiska grundvetenskaper; Mice; Natural Sciences; Naturvetenskap; Oxidation-Reduction; Protein translation; Proteome/metabolism; Proteomics; Redox proteomics; Research Paper; Sulfhydryl Compounds; Redox proteomics; Hematopoiesis; Developmental biology; Cysteine oxidative modifications; Leukemia; MLL-ENL; HSPCs; Cys; Protein translation
• ISSN: 2213-2317; 2213-2317
• DOI: 10.1016/j.redox.2022.102343

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.