Mass-Cytometry-Based Quantification of Global Histone Post-Translational Modifications at Single-Cell Resolution Across Peripheral Immune Cells in IBD.

Humans Histones / metabolism Leukocytes, Mononuclear / metabolism Case-Control Studies Inflammatory Bowel Diseases Colitis, Ulcerative Protein Processing, Post-Translational
Single-cell epigenetic crohn's disease histone modifications inflammatory bowel disease ulcerative colitis

Journal

Journal of Crohn's & colitis
ISSN: 1876-4479
Titre abrégé: J Crohns Colitis
Pays: England
ID NLM: 101318676

Informations de publication

Date de publication:
03 May 2023
Historique:
medline: 5 5 2023
pubmed: 27 12 2022
entrez: 26 12 2022
Statut: ppublish

Résumé

Current understanding of histone post-translational modifications [histone modifications] across immune cell types in patients with inflammatory bowel disease [IBD] during remission and flare is limited. The present study aimed to quantify histone modifications at a single-cell resolution in IBD patients during remission and flare and how they differ compared to healthy controls. We performed a case-control study of 94 subjects [83 IBD patients and 11 healthy controls]. IBD patients had either ulcerative colitis [n = 38] or Crohn's disease [n = 45] in clinical remission or flare. We used epigenetic profiling by time-of-flight [EpiTOF] to investigate changes in histone modifications within peripheral blood mononuclear cells from IBD patients. We discovered substantial heterogeneity in histone modifications across multiple immune cell types in IBD patients. They had a higher proportion of less differentiated CD34+ haematopoietic progenitors, and a subset of CD56bright natural killer [NK] cells and γδ T cells characterized by distinct histone modifications associated with gene transcription. The subset of CD56bright NK cells had increases in several histone acetylations. An epigenetically defined subset of NK cells was associated with higher levels of C-reactive protein in peripheral blood. CD34+ monocytes from IBD patients had significantly decreased cleaved H3T22, suggesting they were epigenetically primed for macrophage differentiation. We describe the first systems-level quantification of histone modifications across immune cells from IBD patients at a single-cell resolution, revealing the increased epigenetic heterogeneity that is not possible with traditional ChIP-seq profiling. Our data open new directions in investigating the association between histone modifications and IBD pathology using other epigenomic tools.

Sections du résumé

BACKGROUND AND AIMS OBJECTIVE
Current understanding of histone post-translational modifications [histone modifications] across immune cell types in patients with inflammatory bowel disease [IBD] during remission and flare is limited. The present study aimed to quantify histone modifications at a single-cell resolution in IBD patients during remission and flare and how they differ compared to healthy controls.
METHODS METHODS
We performed a case-control study of 94 subjects [83 IBD patients and 11 healthy controls]. IBD patients had either ulcerative colitis [n = 38] or Crohn's disease [n = 45] in clinical remission or flare. We used epigenetic profiling by time-of-flight [EpiTOF] to investigate changes in histone modifications within peripheral blood mononuclear cells from IBD patients.
RESULTS RESULTS
We discovered substantial heterogeneity in histone modifications across multiple immune cell types in IBD patients. They had a higher proportion of less differentiated CD34+ haematopoietic progenitors, and a subset of CD56bright natural killer [NK] cells and γδ T cells characterized by distinct histone modifications associated with gene transcription. The subset of CD56bright NK cells had increases in several histone acetylations. An epigenetically defined subset of NK cells was associated with higher levels of C-reactive protein in peripheral blood. CD34+ monocytes from IBD patients had significantly decreased cleaved H3T22, suggesting they were epigenetically primed for macrophage differentiation.
CONCLUSION CONCLUSIONS
We describe the first systems-level quantification of histone modifications across immune cells from IBD patients at a single-cell resolution, revealing the increased epigenetic heterogeneity that is not possible with traditional ChIP-seq profiling. Our data open new directions in investigating the association between histone modifications and IBD pathology using other epigenomic tools.

Identifiants

DOI: 10.1093/ecco-jcc/jjac194 PMID: 36571819 PMC: PMC10155749
pubmed: 36571819
pii: 6961024
doi: 10.1093/ecco-jcc/jjac194
pmc: PMC10155749
doi:

Substances chimiques

Histones 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

804-815

Subventions

Organisme : NIAID NIH HHS
ID : U19 AI057229
Pays : United States

Informations de copyright

© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.

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Auteurs

Lawrence Bai (L)

Immunology Program, Stanford University School of Medicine, 1215 Welch Road, Modular B, Stanford, CA 94305, USA.

Denis Dermadi (D)

Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA.
Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA 94305, USA.

Laurynas Kalesinskas (L)

Biomedical Informatics Training Program, Stanford University School of Medicine, 1265 Welch Road, MSOB X-343, Stanford, CA 94305, USA.
ORCID: 0000-0002-2903-2378

Mai Dvorak (M)

Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA.
Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.

Sarah E Chang (SE)

Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA.
Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.

Ananthakrishnan Ganesan (A)

Computational and Mathematical Engineering, Stanford University, 475 Via Ortega, Suite B060, Stanford, CA 94305, USA.
ORCID: 0000-0001-6242-4261

Samuel J S Rubin (SJS)

Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.

Alex Kuo (A)

Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA.
Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.

Peggie Cheung (P)

Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA.
Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.

Michele Donato (M)

Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA.
Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA 94305, USA.

Paul J Utz (PJ)

Immunology Program, Stanford University School of Medicine, 1215 Welch Road, Modular B, Stanford, CA 94305, USA.
Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA.
Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.

Aida Habtezion (A)

Immunology Program, Stanford University School of Medicine, 1215 Welch Road, Modular B, Stanford, CA 94305, USA.
Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA.
Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.

Purvesh Khatri (P)

Immunology Program, Stanford University School of Medicine, 1215 Welch Road, Modular B, Stanford, CA 94305, USA.
Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA.
Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
ORCID: 0000-0002-4143-4708

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