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

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...

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Autores principales: Pimkova, K., Jassinskaja, M., Munita, R., Ciesla, M., Guzzi, N., Cao Thi Ngoc, P., Vajrychova, M., Johansson, E., Bellodi, C., Hansson, J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157258/
https://www.ncbi.nlm.nih.gov/pubmed/35640380
http://dx.doi.org/10.1016/j.redox.2022.102343
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author Pimkova, K.
Jassinskaja, M.
Munita, R.
Ciesla, M.
Guzzi, N.
Cao Thi Ngoc, P.
Vajrychova, M.
Johansson, E.
Bellodi, C.
Hansson, J.
author_facet Pimkova, K.
Jassinskaja, M.
Munita, R.
Ciesla, M.
Guzzi, N.
Cao Thi Ngoc, P.
Vajrychova, M.
Johansson, E.
Bellodi, C.
Hansson, J.
author_sort Pimkova, K.
collection PubMed
description 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.
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spelling pubmed-91572582022-06-02 Quantitative analysis of redox proteome reveals oxidation-sensitive protein thiols acting in fundamental processes of developmental hematopoiesis Pimkova, K. Jassinskaja, M. Munita, R. Ciesla, M. Guzzi, N. Cao Thi Ngoc, P. Vajrychova, M. Johansson, E. Bellodi, C. Hansson, J. Redox Biol Research Paper 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. Elsevier 2022-05-23 /pmc/articles/PMC9157258/ /pubmed/35640380 http://dx.doi.org/10.1016/j.redox.2022.102343 Text en © 2022 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Paper
Pimkova, K.
Jassinskaja, M.
Munita, R.
Ciesla, M.
Guzzi, N.
Cao Thi Ngoc, P.
Vajrychova, M.
Johansson, E.
Bellodi, C.
Hansson, J.
Quantitative analysis of redox proteome reveals oxidation-sensitive protein thiols acting in fundamental processes of developmental hematopoiesis
title Quantitative analysis of redox proteome reveals oxidation-sensitive protein thiols acting in fundamental processes of developmental hematopoiesis
title_full Quantitative analysis of redox proteome reveals oxidation-sensitive protein thiols acting in fundamental processes of developmental hematopoiesis
title_fullStr Quantitative analysis of redox proteome reveals oxidation-sensitive protein thiols acting in fundamental processes of developmental hematopoiesis
title_full_unstemmed Quantitative analysis of redox proteome reveals oxidation-sensitive protein thiols acting in fundamental processes of developmental hematopoiesis
title_short Quantitative analysis of redox proteome reveals oxidation-sensitive protein thiols acting in fundamental processes of developmental hematopoiesis
title_sort quantitative analysis of redox proteome reveals oxidation-sensitive protein thiols acting in fundamental processes of developmental hematopoiesis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157258/
https://www.ncbi.nlm.nih.gov/pubmed/35640380
http://dx.doi.org/10.1016/j.redox.2022.102343
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