Georges Lacaud: Haematopoietic cells are generated from a haemogenic endothelium through a Runx1 dependent process

Haematopoietic cells are generated from a haemogenic endothelium through a Runx1 dependent process

Christophe Lancrin, Patrycja Scroczynska, Valerie Kouskoff, Georges Lacaud Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK glacaud@picr.man.ac.uk

Two major theories of the cellular origin of haematopoietic cells have been advanced. In the first one, haematopoietic cells arise from a mesodermal progenitor with both endothelial and haematopoietic potential called the haemangioblast. The other conflicting theory instead associates the first haematopoietic cells with a phenotypically differentiated endothelial cell with haematopoietic potential, i.e. a haemogenic endothelium. Support for the haemangioblast concept was initially provided by the identification a clonal precursor which gives rise after 4 days to blast colonies with both endothelial and haematopoietic. We performed a series of studies to determine the cellular and molecular events leading to the generation of blast colony from BL-CFC. Our data demonstrate that the haemangioblast generates haematopoietic cells through the formation of a haemogenic endothelium intermediate, providing the first direct link between these two precursor populations. This haemogenic endothelial cell population is transiently generated during blast development and is also detected in gastrulating embryos. At the molecular level, we have demonstrated that the transcription factor SCL/TAL1 is indispensable for the establishment of this haemogenic endothelium cell population from the haemangioblast whereas RUNX1/AML1 is critical for generation of haematopoietic cells from this haemogenic endothelium. These results indicate that the two a priori conflicting theories on the origin of haematopoietic development, haemangioblast and haemogenic endothelium, can be merged into a single linear developmental process leading to the formation of the first committed haematopoietic precursors.