Epigenetic and gene expression variation are linked to phenotypic differences both within [1] and across species [2,3]. Within the hematopoietic system, multiple studies have identified both conserved as well as species-specific patterns of chromatin accessibility [4,5] and/or gene expression among mammals [5,6,7]. Using a combination of publicly available [8-12] and newly generated multi-omics datasets (i.e., ATAC-seq and RNA-seq) either at the single-cell and/or bulk level, we have started investigating the molecular differences within the major hematopoietic cells lineages across 4 vertebrate species (i.e., human, mouse, chicken and zebrafish). By comparing the patterns of expression of a set of 8,884 orthologous genes, we identified hundreds of lineage-specific genes showing high correlation of expression across vertebrates. Next, we begun to identify orthologous DNA accessible elements and investigate whether they might regulate the same genes across species. By linking functional and gene expression conservation across species, we will identify a set of candidate DNA regulatory elements active within the human genome and within each of our hematopoietic cell lineages that we will functionally validate in vitro.