LAUSR

Studies of human erythropoiesis have relied, for the most part, on the in vitro differentiation of hematopoietic stem and progenitor cells (HSPC) from different sources. Here, we report that despite the common core erythroid program that exists between cord blood (CB)‐ and peripheral blood (PB)‐HSPC induced toward erythroid differentiation in vitro, significant functional differences exist. We undertook a comparative analysis of human erythropoiesis using these two different sources of HSPC. Upon in vitro erythroid differentiation, CB‐derived cells proliferated 4‐fold more than PB‐derived cells. However, CB‐derived cells exhibited a delayed kinetics of differentiation, resulting in an increased number of progenitors, notably colony‐forming unit (CFU‐E). The phenotypes of early erythroid differentiation stages also differed between the two sources with a significantly higher percentage of IL3R‐GPA‐CD34+CD36+ cells generated from PB‐ than CB‐HSPCs. This subset was found to generate both burst‐forming unit (BFU‐E) and CFU‐E colonies in colony‐forming assays. To further understand the differences between CB‐ and PB‐HSPC, cells at eight stages of erythroid differentiation were sorted from each of the two sources and their transcriptional profiles were compared. We document differences at the CD34, BFU‐E, poly‐ and orthochromatic stages. Genes exhibiting the most significant differences in expression between HSPC sources clustered into cell cycle‐ and autophagy‐related pathways. Altogether, our studies provide a qualitative and quantitative comparative analysis of human erythropoiesis, highlighting the impact of the developmental origin of HSPCs on erythroid differentiation.