During vertebrate development, several waves of haematopoiesis take place in different regions of the embryo. For example, studies from the mouse have shown that erythro myeloid progenitors develop from endothelial intermediates in yolk sac. Studying human blood cell development in vivo, however, is not possible using genetic methods. Now, Andrew Elefanty and colleagues employ human pluripotent stem cells in a blast colony-forming cell assay to model the emergence of vascular and haematopoietic lineages. Using transgenic reporters for SOX17 to label endothelium and RUNX1C to label haematopoietic progenitor cells, the authors show through live imaging that the major source of blood cells is from a SOX17− endothelial progenitor. The CD43+ blood cells derived from these SOX17− haemangioblast-like cells express higher levels of key factors such as RUNX1, GFI1 and SPI1, indicating greater haematopoietic potential than blood derived from SOX17+ cells. Next, the researchers show the crucial role of RUNX1 for haematopoiesis in this system, because RUNX1-KO cultures generate only a single wave of yolk sac-like erythropoiesis. Moreover, this erythropoiesis is dependent on GFI1, indicating that GFI1 is required both upstream and downstream of RUNX1. These results provide new insights into, and a tractable system for, the study of human yolk sac-like haematopoiesis.
- © 2020. Published by The Company of Biologists Ltd