Emergence of haematopoietic stem cells during development

Abstract

Self-renewable haematopoietic stem cells (HSCs) become segregated during development into a finite pool, from which they are mobilized upon physiological requirement. A central feature characterizing developmental haematopoiesis is that definitive organs become colonized by HSCs originating from a central source. The emission of HSCs occurs more or less continuously during a protracted period in parallel or successive sites. The most recently discovered of these sites is the placenta. The allantois, which is one of the components of the placenta, probed before it becomes vascularised, turns out to be a location where clonogenic precursors become committed. The placenta is thus a site of intrinsic haematopoiesis. Until this finding, the aorta and periaortic tissues were held to be the sites of definitive HSC commitment. The haematopoietic process in the aorta is prominent, particularly in avian embryos, and displays striking anatomical relationships between endothelial and haematopoietic cells. This made it possible to investigate the cytological and molecular relationship between the two types of cells. Somite exchanges between quail and chicken disclosed two distinct lineages, a dorsal one, purely endothelial, and a ventral one, hemangioblastic. The latter, also termed hemogenic endothelium, builds at first the whole inside lining of the aorta, and is then progressively replaced by cells of somitic origin, beginning with the aortic roof; it emits haematopoietic cells when located in the floor of the aorta and disappears. These events involve a changing molecular pattern, with expressions of transcription factor Runx1 and receptor VEGF-R2 as faithful markers of the lineage switch. Taking advantage of the stereotyped anatomical arrangement at the aortic level, which is favourable to dissect the mechanisms of HSC commitment, the analysis of developmental haematopoiesis should progress still further.