The meta-epigenomic structure of purified human stem cell populations is defined at cis-regulatory sequences

N. Ari Wijetunga, Fabien Delahaye, Yong M. Zhao, Aaron Golden, Jessica C. Mar, Francine H. Einstein, John M. Greally

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

The mechanism and significance of epigenetic variability in the same cell type between healthy individuals are not clear. Here we purify human CD34+ haematopoietic stem and progenitor cells (HSPCs) from different individuals and find that there is increased variability of DNA methylation at loci with properties of promoters and enhancers. The variability is especially enriched at candidate enhancers near genes transitioning between silent and expressed states, and encoding proteins with leukocyte differentiation properties. Our findings of increased variability at loci with intermediate DNA methylation values, at candidate poised enhancers and at genes involved in HSPC lineage commitment suggest that CD34+ cell subtype heterogeneity between individuals is a major mechanism for the variability observed. Epigenomic studies performed on cell populations, even when purified, are testing collections of epigenomes, or meta-epigenomes. Our findings show that meta-epigenomic approaches to data analysis can provide insights into cell subpopulation structure.

Original languageEnglish (US)
Article number5195
JournalNature communications
Volume5
DOIs
StatePublished - Oct 20 2014

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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