γH2AX in mouse embryonic stem cells: Distribution during differentiation and following γ-irradiation.

Autor: Karagiannis TC; Epigenetics in Human Health and Disease Program, Baker Heart and Diabetes Institute, 75 Commercial Road, Prahran, VIC 3004, Australia; Epigenomic Medicine Laboratory at prospED Training, Carlton, VIC 3053, Australia; Department of Clinical Pathology, The University of Melbourne, Parkville, VIC 3010, Australia; Department of Microbiology and Immunology, The University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: karat@unimelb.edu.au., Orlowski C; Epigenetics in Human Health and Disease Program, Baker Heart and Diabetes Institute, 75 Commercial Road, Prahran, VIC 3004, Australia., Ververis K; Epigenomic Medicine Laboratory at prospED Training, Carlton, VIC 3053, Australia; Department of Clinical Pathology, The University of Melbourne, Parkville, VIC 3010, Australia., Pitsillou E; Epigenomic Medicine Laboratory at prospED Training, Carlton, VIC 3053, Australia; School of Science, STEM College, RMIT University, VIC 3001, Australia., Sarila G; Epigenetics in Human Health and Disease Program, Baker Heart and Diabetes Institute, 75 Commercial Road, Prahran, VIC 3004, Australia., Keating ST; Epigenetics in Human Health and Disease Program, Baker Heart and Diabetes Institute, 75 Commercial Road, Prahran, VIC 3004, Australia., Foong LJ; Epigenomic Medicine Laboratory at prospED Training, Carlton, VIC 3053, Australia., Fabris S; Epigenomic Medicine Laboratory at prospED Training, Carlton, VIC 3053, Australia., Ngo-Nguyen C; Epigenomic Medicine Laboratory at prospED Training, Carlton, VIC 3053, Australia., Malik N; Epigenomic Medicine Laboratory at prospED Training, Carlton, VIC 3053, Australia., Okabe J; Epigenetics in Human Health and Disease Program, Baker Heart and Diabetes Institute, 75 Commercial Road, Prahran, VIC 3004, Australia., Hung A; School of Science, STEM College, RMIT University, VIC 3001, Australia., Mantamadiotis T; Department of Microbiology and Immunology, The University of Melbourne, Parkville, VIC 3010, Australia; Department of Surgery (RMH), The University of Melbourne, Parkville, VIC 3010, Australia., El-Osta A; Epigenetics in Human Health and Disease Program, Baker Heart and Diabetes Institute, 75 Commercial Road, Prahran, VIC 3004, Australia; Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Sha Tin, Hong Kong; Hong Kong Institute of Diabetes and Obesity, Prince of Wales Hospital, The Chinese University of Hong Kong, 3/F Lui Che Woo Clinical Sciences Building, 30-32 Ngan Shing Street, Sha Tin, Hong Kong; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong; Biomedical Laboratory Science, Department of Technology, Faculty of Health, University College Copenhagen, Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: Cells & development [Cells Dev] 2024 Mar; Vol. 177, pp. 203882. Date of Electronic Publication: 2023 Nov 11.
DOI: 10.1016/j.cdev.2023.203882
Abstrakt: Phosphorylated histone H2AX (γH2AX) represents a sensitive molecular marker of DNA double-strand breaks (DSBs) and is implicated in stem cell biology. We established a model of mouse embryonic stem cell (mESC) differentiation and examined the dynamics of γH2AX foci during the process. Our results revealed high numbers of γH2AX foci in undifferentiated mESCs, decreasing as the cells differentiated towards the endothelial cell lineage. Notably, we observed two distinct patterns of γH2AX foci: the typical discrete γH2AX foci, which colocalize with the transcriptionally permissive chromatin mark H3K4me3, and the less well-characterized clustered γH2AX regions, which were only observed in intermediate progenitor cells. Next, we explored responses of mESCs to γ-radiation ( 137 Cs). Following exposure to γ-radiation, mESCs showed a reduction in cell viability and increased γH2AX foci, indicative of radiosensitivity. Despite irradiation, surviving mESCs retained their differentiation potential. To further exemplify our findings, we investigated neural stem progenitor cells (NSPCs). Similar to mESCs, NSPCs displayed clustered γH2AX foci associated with progenitor cells and discrete γH2AX foci indicative of embryonic stem cells or differentiated cells. In conclusion, our findings demonstrate that γH2AX serves as a versatile marker of DSBs and may have a role as a biomarker in stem cell differentiation. The distinct patterns of γH2AX foci in differentiating mESCs and NSPCs provide valuable insights into DNA repair dynamics during differentiation, shedding light on the intricate balance between genomic integrity and cellular plasticity in stem cells. Finally, the clustered γH2AX foci observed in intermediate progenitor cells is an intriguing feature, requiring further exploration.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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