Abstract 430: An Acyltransferase Controls The Generation Of Hematopoietic And Endothelial Lineages In Zebrafish And Mouse ES Cells
Blood cells and blood vessels develop from a common progenitor, the hemangioblast. The molecular pathway that controls the specification of such a stem cell remains elusive. Here we show that a lysocardiolipin acyltransferase, lycat, is critical for the establishment of both hematopoietic and endothelial lineages. We isolated lycat by positional cloning from the genetic interval of cloche, a zebrafish mutant lacking both blood cells and blood vessels. Reduction of lycat mRNA levels in wild-type zebrafish embryos abolishes both endothelial and hematopoietic lineages. lycat mRNA rescues blood lineages in zebrafish cloche mutant embryos. E165R and G166L mutations in the highly conserved catalytic domain in Lycat abolish its function in zebrafish hematopoiesis. Lycat acts upstream of scl and etsrp in zebrafish hemangioblast development. The forced mouse Lycat transgene leads to increased mRNA expression of hematopoietic and endothelial genes as well as increased blast colonies and their progenies, endothelial and hematopoietic lineages while the mouse Lycat siRNA transgene leads to a decrease expression of hematopoietic and endothelial genes during ES cell differentiation. Therefore, Lycat is the earliest known player in generation of the hemangioblast.