title: The meta-epigenomic structure of purified human stem cell populations is defined at cis-regulatory sequences.
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.
authors.affiliation: Center for Epigenomics and Department of Genetics (Division of Computational Genetics), Albert Einstein College of Medicine, 1301 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: N Ari
authors.initials: NA
authors.lastname: Wijetunga
authors.affiliation: Department of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine, 1301 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Fabien
authors.initials: F
authors.lastname: Delahaye
authors.affiliation: Department of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine, 1301 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Yong Mei
authors.initials: YM
authors.lastname: Zhao
authors.affiliation: Center for Epigenomics and Department of Genetics (Division of Computational Genetics), Albert Einstein College of Medicine, 1301 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Golden
authors.affiliation: Department of Computational and Systems Biology, Albert Einstein College of Medicine, 1301 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Mar
authors.affiliation: Department of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine, 1301 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Francine H
authors.initials: FH
authors.lastname: Einstein
authors.affiliation: Center for Epigenomics and Department of Genetics (Division of Computational Genetics), Albert Einstein College of Medicine, 1301 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Greally
mesh_terms: D000465:Algorithms; D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002843:Chromatin / Q000737:chemistry; D002874:Chromosome Mapping; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006657:Histones / Q000737:chemistry; D006801:Humans; D007962:Leukocytes / Q000166:cytology; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D013234:Stem Cells / Q000166:cytology*
chemical_list: D018952:Antigens, CD34; D002843:Chromatin; D006657:Histones