Single-Cell Chromatin Modification Profiling Reveals Increased Epigenetic Variations with Aging
Peggie Cheung, Francesco Vallania, Hayley C Warsinske, Michele Donato, Steven Schaffert, Sarah E Chang, Mai Dvorak, Cornelia L Dekker, Mark M Davis, Paul J Utz, Purvesh Khatri, Alex J Kuo, Peggie Cheung, Francesco Vallania, Hayley C Warsinske, Michele Donato, Steven Schaffert, Sarah E Chang, Mai Dvorak, Cornelia L Dekker, Mark M Davis, Paul J Utz, Purvesh Khatri, Alex J Kuo
Abstract
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: ClinicalTrials.gov NCT01987349 NCT03022396 NCT03022422.
Keywords: Epigenetics; aging; cell identity; chromatin modifications; heritability; histones; immune system; mass cytometry; transcriptional noise; twins.
Conflict of interest statement
Declaration of Interests
The authors declare no competing interests.
Copyright © 2018 Elsevier Inc. All rights reserved.
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Source: PubMed