PT  - JOURNAL ARTICLE
AU  - N. Ari Wijetunga
AU  - Fabien Delahaye
AU  - Yong Mei Zhao
AU  - Aaron Golden
AU  - Jessica C. Mar
AU  - Francine H. Einstein
AU  - John M. Greally
TI  - The meta-epigenomic structure of purified human stem cell populations is defined at <em>cis</em>-regulatory sequences
AID  - 10.1101/007591
DP  - 2014 Jan 01
TA  - bioRxiv
PG  - 007591
4099  - http://biorxiv.org/content/early/2014/08/01/007591.short
4100  - http://biorxiv.org/content/early/2014/08/01/007591.full
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.