ITERATIVE AND PLEIOTROPIC ROLES OF ENDOTHELIAL CELLS IN HUMAN HEMATOPOIETIC ERYTHROPOIESIS

Abstract

Local tissue microenvironments regulate directly the hematopoietic development and cell fate specification of both stem cells and lineage-committed progenitor cells. The identification of hematopoietic niches and the mechanisms by which they regulate cell fate specification offers the opportunity to better understand tissue homeostasis and regeneration. Hematopoietic stem cells (HSCs) and lineage-committed progenitor cells are closely associated with blood vessels during hematopoietic development. Recent studies have confirmed the essential role of endothelial cells (ECs) in the maintenance and lineage-specification of HSCs. However, the precise mechanisms through which ECs regulate hematopoietic development are not well understood. Particularly, we know little about which stage in the development ECs regulate hematopoietic progenitor cells. Here we identified that ECs promote erythropoiesis in a pleiotropic and iterative manner. We cultured CD34+ human hematopoietic stem and progenitor cells (HSPCs) in the presence of vascular ECs. Following in vitro differentiation, we measured the number of various lineage cells using surface marker detection. Among hematopoietic cells, we found that both CD34+CD38- HSPCs and CD71+CD235A+ erythroblasts were increased. Transwell culture system validated that ECs facilitate erythropoiesis via soluble factors. Noteworthy, primitive ECs derived from pluripotent stem cells increased the number of HSPCs, while mature ECs derived from umbilical cord increased the number of erythroblasts. The results demonstrate that primitive and mature ECs facilitate erythropoiesis at both the HSPC and erythroblast level, respectively, and suggest that the chronicity of hematopoiesis matches the niche. Our study proposes iterative and pleiotropic roles of ECs in human hematopoietic erythropoiesis.