An in vitro model of human hematopoiesis identifies a regulatory role for the aryl hydrocarbon receptor

An in vitro model of human hematopoietic stem cell differentiation is found to allow development of multiple immune lineages through use of single-cell methods. Using this model, we demonstrate that activation of aryl hydrocarbon receptor (AHR) signaling drives human hematopoietic stem and progenitor cells (HSPCs) to differentiate towards myeloid lineages at the expense of lymphoid lineages. Gene perturbations in progenitor cells and lineage-specified immune cells by AHR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are identified. Overall design: Human cord-blood derived CD34+ HSPCs were cultured over a 28-day period in vitro in media enriched with cytokines/growth factors and treated with either the control vehicle (0.02% DMSO) or 1 nM TCDD. Cells were harvested on day 0 and every 7 days from both the vehicle and TCDD-treated experimental groups and sequenced at a single cell level for a total of 5 kinetic endpoints.