Identifier des signaux moléculaires du micro-environnement de l'aorte conduisant à l'émergence des HSPC

Hematopoietic stem cells (HSCs) are a rare group of cells with the unique ability to self-renew and stay undifferentiated. They originate from hemogenic endothelial cells (HECs), which are specified during a brief developmental window, primarily on the ventral side of the aorta. The dorso-ventral polarization of HECs is influenced by anatomical and molecular signals from surrounding structures like the notochord and intermediate mesoderm, though the precise mechanisms are still unclear. To explore this, I used the avian model to study how different structures impact HEC polarization. During my PhD, I focused on this polarization by performing microsurgical removal of the notochord and neural tube in chicken embryos at E2, before the onset of endothelial to hematopoietic transition (EHT). I analyzed embryos at E3 and E4. Disruption of the microenvironment by removing these structures led to the emergence of HECs within 24 hours, but by E4, the embryos showed signs of recovery, with only a few Runx1-expressing cells. Additionally, I carried out quail-chicken chimera grafts to manipulate the microenvironment and shift the polarization behavior of the aorta. I observed the ectopic emergence of HECs on the dorsal side when the intermediate mesoderm was grafted in place of the notochord. To further confirm that the dorsal appearance of Runx1+ cells was due to the ablation itself, I grafted 3- 5 neutral blue beads in place of the notochord and neural tube. This experiment demonstrated that the structure of the aorta remained intact, allowing for future molecular manipulations. By soaking these beads with specific molecules involved in HEC polarity, I plan to observe how the microenvironment is altered and further understand the key signals driving HEC emergence.