RT Journal Article SR Electronic T1 The meta-epigenomic structure of purified human stem cell populations is defined at cis-regulatory sequences JF bioRxiv FD Cold Spring Harbor Laboratory SP 007591 DO 10.1101/007591 A1 N. Ari Wijetunga A1 Fabien Delahaye A1 Yong Mei Zhao A1 Aaron Golden A1 Jessica C. Mar A1 Francine H. Einstein A1 John M. Greally YR 2014 UL http://biorxiv.org/content/early/2014/08/01/007591.abstract AB The mechanism and significance of epigenetic variability in the same cell type between healthy individuals are not clear. Here, we purify human CD34+ hematopoietic 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.