Single-Cell Chromatin Modification Profiling Reveals Increased Epigenetic Variations with Aging

Cell. 2018 May 31;173(6):1385-1397.e14. doi: 10.1016/j.cell.2018.03.079. Epub 2018 Apr 26.


Post-translational modifications of histone proteins and exchanges of histone variants of chromatin are central to the regulation of nearly all DNA-templated biological processes. However, the degree and variability of chromatin modifications in specific human immune cells remain largely unknown. Here, we employ a highly multiplexed mass cytometry analysis to profile the global levels of a broad array of chromatin modifications in primary human immune cells at the single-cell level. Our data reveal markedly different cell-type- and hematopoietic-lineage-specific chromatin modification patterns. Differential analysis between younger and older adults shows that aging is associated with increased heterogeneity between individuals and elevated cell-to-cell variability in chromatin modifications. Analysis of a twin cohort unveils heritability of chromatin modifications and demonstrates that aging-related chromatin alterations are predominantly driven by non-heritable influences. Together, we present a powerful platform for chromatin and immunology research. Our discoveries highlight the profound impacts of aging on chromatin modifications.

Trial registration: NCT01987349 NCT03022396 NCT03022422.

Keywords: Epigenetics; aging; cell identity; chromatin modifications; heritability; histones; immune system; mass cytometry; transcriptional noise; twins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aging*
  • Cell Lineage
  • Cell Separation
  • Chromatin / chemistry*
  • Diseases in Twins
  • Epigenesis, Genetic*
  • Female
  • Flow Cytometry
  • Histones / metabolism
  • Humans
  • Immune System
  • Immunophenotyping
  • Leukocytes, Mononuclear / cytology
  • Male
  • Middle Aged
  • Monocytes / cytology
  • Principal Component Analysis
  • Protein Processing, Post-Translational
  • Registries
  • Young Adult


  • Chromatin
  • Histones

Associated data