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Crosstalk of Histone Modifications in the Healthy Human Immune System

View ORCID ProfileDenis Dermadi, Laurynas Kalesinskas, Ananthakrishnan Ganesan, Alex Kuo, Peggie Cheung, Sarah Cheng, Mei Dvorak, View ORCID ProfileThomas J. Scriba, Aida Habtezion, Michele Donato, Paul J. Utz, View ORCID ProfilePurvesh Khatri
doi: https://doi.org/10.1101/2022.01.21.477300
Denis Dermadi
1Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, CA 94305, USA
2Center for Biomedical Informatics Research, Department of Medicine, School of Medicine, Stanford University, Stanford, CA 94305, USA
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  • ORCID record for Denis Dermadi
Laurynas Kalesinskas
1Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, CA 94305, USA
2Center for Biomedical Informatics Research, Department of Medicine, School of Medicine, Stanford University, Stanford, CA 94305, USA
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Ananthakrishnan Ganesan
1Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, CA 94305, USA
2Center for Biomedical Informatics Research, Department of Medicine, School of Medicine, Stanford University, Stanford, CA 94305, USA
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Alex Kuo
1Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, CA 94305, USA
3Division of Immunology and Rheumatology, Department of Medicine, School of Medicine, Stanford University, Stanford, CA 94305, USA
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Peggie Cheung
1Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, CA 94305, USA
3Division of Immunology and Rheumatology, Department of Medicine, School of Medicine, Stanford University, Stanford, CA 94305, USA
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Sarah Cheng
1Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, CA 94305, USA
3Division of Immunology and Rheumatology, Department of Medicine, School of Medicine, Stanford University, Stanford, CA 94305, USA
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Mei Dvorak
1Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, CA 94305, USA
3Division of Immunology and Rheumatology, Department of Medicine, School of Medicine, Stanford University, Stanford, CA 94305, USA
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Thomas J. Scriba
4South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, 7925, South Africa
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Aida Habtezion
1Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, CA 94305, USA
5Stanford University School of Medicine, Division of Gastroenterology and Hepatology, Stanford, CA 94305, USA
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Michele Donato
1Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, CA 94305, USA
2Center for Biomedical Informatics Research, Department of Medicine, School of Medicine, Stanford University, Stanford, CA 94305, USA
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Paul J. Utz
1Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, CA 94305, USA
3Division of Immunology and Rheumatology, Department of Medicine, School of Medicine, Stanford University, Stanford, CA 94305, USA
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  • For correspondence: pkhatri@stanford.edu pjutz@stanford.edu
Purvesh Khatri
1Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, CA 94305, USA
2Center for Biomedical Informatics Research, Department of Medicine, School of Medicine, Stanford University, Stanford, CA 94305, USA
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  • ORCID record for Purvesh Khatri
  • For correspondence: pkhatri@stanford.edu pjutz@stanford.edu
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ABSTRACT

Chromatin remodeling through post-translational modifications of histone tails (HPTM) is fundamental for regulation and maintenance of DNA-centered processes. Systems level understanding of coordination and interactions between HPTMs and their impact on the functional state of the immune cells remain unexplored due to the technical reasons. We leveraged large biologically heterogeneous data (>27 million cells), comprising of primary human immune cells profiled for 33 HPTMs and 4 histone variants at the single-cell level using high-dimensional mass cytometry (EpiTOF), to discover and map relations between HPTMs at the systems level. Briefly, we elucidated a comprehensive epigenetic network of HPTM interactions, discovered a novel subset of hematopoietic progenitors with distinct epigenetic profile, and revealed hitherto undescribed associations between a decrease in global methylations, modulation of one-carbon metabolism, and immune cell life span. Ultimately our work lays a foundation for future studies aimed at understanding complexity of HPTM interactions in immune response in infectious or autoimmune diseases, cancers, and vaccination.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵* Co-first authors

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Posted January 23, 2022.
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Crosstalk of Histone Modifications in the Healthy Human Immune System
Denis Dermadi, Laurynas Kalesinskas, Ananthakrishnan Ganesan, Alex Kuo, Peggie Cheung, Sarah Cheng, Mei Dvorak, Thomas J. Scriba, Aida Habtezion, Michele Donato, Paul J. Utz, Purvesh Khatri
bioRxiv 2022.01.21.477300; doi: https://doi.org/10.1101/2022.01.21.477300
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Crosstalk of Histone Modifications in the Healthy Human Immune System
Denis Dermadi, Laurynas Kalesinskas, Ananthakrishnan Ganesan, Alex Kuo, Peggie Cheung, Sarah Cheng, Mei Dvorak, Thomas J. Scriba, Aida Habtezion, Michele Donato, Paul J. Utz, Purvesh Khatri
bioRxiv 2022.01.21.477300; doi: https://doi.org/10.1101/2022.01.21.477300

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