New insights into the endothelial-to-hematopoietic transition generating hematopoietic stem and progenitor cells

Orateur : Thierry JAFFREDO (CNRS UMR 7622, Université Sorbonne, Paris)

Hematopoietic Stem and Progenitor Cells (HSPCs) are at the basis of the regulated functioning of the hematopoietic system throughout the life of the individual. In adult amniotes, HSPCs reside in the bone marrow but are produced very early during development, transiently and in small numbers, at the level the dorsal aorta from specialized endothelial cells (EC), termed hemogenic, themselves derived from non-hemogenic ECs. Hemogenic ECs, under the influence of signals yet to be defined, lose their endothelial fate and acquire a hematopoietic identity through a mechanism designated as endothelial-to-hematopoietic transition (EHT). How hemogenic ECs are specified and for how long during development and how EHT is fine-tuned allowing HSPC formation remain unanswered questions with major implications in regenerative medicine. HSPC generation via EHT is thought to be restricted to the early stages of development. By using experimental embryology and genetic approaches in birds and mice respectively, we document the discovery of a bone marrow (BM) hemogenic endothelium in the late foetus/young adult. These cells are capable of de novo producing a cohort of HSPCs in situ that harbor a very specific molecular signature close to that of aortic ECs undergoing EHT or their immediate progenies i.e. recently emerged HSPCs and are shown capable of undergoing EHT in vitro (Yvernogeau et al., Nature Cell Biology, 2019). Our results reveal that HSPCs can be generated de novo past embryonic stages. Taken together our results should help to better define essential steps in the commitment towards HSPC to further produce safe and robust cells for therapeutic purposes.

Télécharger dans mon agenda