Mass-Cytometry-Based Quantification of Global Histone Post-Translational Modifications at Single-Cell Resolution...

Area of Science:

• Immunology
• Epigenetics
• Cell Biology

Background:

• Limited understanding of histone modifications in immune cells during inflammatory bowel disease (IBD).
• Need to investigate immune cell epigenetic heterogeneity in IBD remission and flare.
• Focus on single-cell resolution for precise analysis.

Purpose of the Study:

• Quantify histone modifications in immune cells of IBD patients at single-cell resolution.
• Compare epigenetic profiles between IBD patients (remission/flare) and healthy controls.
• Identify cell-type-specific histone modification patterns in IBD.

Main Methods:

• Case-control study involving 83 IBD patients and 11 healthy controls.
• Epigenetic profiling by time-of-flight (EpiTOF) used for histone modification analysis.
• Peripheral blood mononuclear cells (PBMCs) analyzed from IBD patients with ulcerative colitis or Crohn's disease.

Main Results:

• Substantial heterogeneity in histone modifications observed across immune cell types in IBD patients.
• Increased proportion of CD34+ hematopoietic progenitors and distinct CD56bright natural killer (NK) and γδ T cell subsets identified.
• CD56bright NK cells showed increased histone acetylations, linked to higher C-reactive protein.
• Decreased cleaved H3T22 in CD34+ monocytes suggests epigenetic priming for macrophage differentiation.

Conclusions:

• First systems-level quantification of histone modifications in IBD immune cells at single-cell resolution.
• Revealed increased epigenetic heterogeneity not detectable by traditional ChIP-seq.
• Data suggest new avenues for investigating histone modifications in IBD pathology using epigenomic tools.