A Unique Epigenomic Landscape Defines Human Erythropoiesis (RNA-seq)

Mammalian erythropoiesis yields a highly specialized cell type, the mature erythrocyte, evolved to meet organismal needs of increased oxygen carrying capacity. To better understand regulation of erythropoiesis, we performed genome-wide chromatin accessibility studies, DNA methylation studies, and transcriptome analyses and correlated this with genomic organization in highly purified populations of primary human erythroid cells across the stages of erythroid development and differentiation. Gene expression patterns and chromatin state dynamics differed significantly between erythroid stages, with significant transitions between some stages indicating cell stage-specific gene regulation during erythropoiesis is a stepwise and hierarchical process involving many cis-regulatory elements. Numerous erythroid-specific, nonpromoter sites of chromatin accessibility were identified, many linked to erythroid cell phenotypic variation and inherited disease. A limited number of sites of chromatin accessibility identified in hematopoietic stem and progenitor cells were also identified in cells committed to the erythroid lineage, demonstrating limited early chromatin priming of erythroid genes during hematopoiesis. Chromatin accessibility of terminally differentiating erythroid cells defined a unique subset of highly specialized cells vastly dissimilar from other hematopoietic cell types. These epigenetic and transcriptome data are powerful tools to study human erythropoiesis Overall design: Erythroid cell culture of human umbilical cord derived CD34+ human hematopoietic stem and progenitor cells (HSPCs) and fluorescence-activated cell sorting to purify discrete populations of progenitor cells at differing stages of erythroid development and differentiation were performed on three replicate sets of cells. RNA-sequencing was then performed on the purified cells. Single end 51 base reads were obtained on an Illumina HiSeq 2500 sequencer. The data is similar to GSE61566 but with higher quality.