The aryl hydrocarbon receptor directs hematopoietic progenitor cell expansion and differentiation.

摘要: The evolutionarily conserved aryl hydrocarbon receptor (AhR) has been studied for its role in environmental chemical-induced toxicity. However, recent studies have demonstrated that the AhR may regulate hematopoietic and immune systems during development a cell-specific manner. These results, together with absence of an vitro model system enabling production large numbers primary human progenitor cells (HPs) capable differentiating into megakaryocyte- erythroid-lineage cells, motivated us to determine if modulation could facilitate both cell expansion megakaryocyte erythroid differentiation. Using novel, pluripotent stem cell–based, chemically-defined, serum feeder cell–free culture system, we show is expressed HPs that, remarkably, activation drives unprecedented HPs, megakaryocyte-lineage cells. Further within rapidly expanding populations directs fate, chronic agonism permissive differentiation acute antagonism favoring specification. results highlight new Good Manufacturing Practice–compliant platform generating virtually unlimited which scrutinize red blood platelet development, including assessment critical fate decisions hematopoiesis.