Aorta-gonad-mesonephros - Haematopoietic Stem Cell Development - Runx1

Runx1

RUNX1 (also known as AML1) is a transcription factor that has been heavily implicated in the production and activation of haemogenic endothelial cells in the AGM. RUNX1 knockout studies have shown a complete removal of definitive haematopoietic activity in all foetal tissues before embryo lethality at E12. RUNX1 knockouts also produce morphological changes in the AGM, with excessive crowding of mesenchymal cells. As mesenchymal cells differentiate into endothelial cells, the absence of RUNX1 may impact on the ability of mesenchymal cells to differentiate into haemogenic endothelial cells. This would explain the increase in mesenchymal cell number, and the distinct lack of cells positive for other haematopoietic markers. Runx1 has also been implicated in the activation of haemogenic endothelium. Using conditional knockouts it was shown that the removal of Runx1 expression in AGM haemogenic endothelial cells, prevented the production of HSCs. The same experiments also showed that once HSCs were produced, Runx1 was no longer required producing no deviation in HSC activity compared to controls. Additionally, When AGM cells from Runx1 knockouts underwent retroviral transfer in vitro to overexpress Runx1, they were able to be rescued and produce definitive haematopoietic cells. This suggests that Runx1 plays a critical role in the signalling pathway for haemogenic cell activation and its production from mesenchymal cells.