Trim33 conditions the lifespan of primitive macrophages and onset of definitive macrophage production

ABSTRACT TRIM33 (Tif1-γ) is a transcriptional regulator notably involved in several aspects of hematopoiesis. It is essential for the production of erythrocytes in zebrafish, and for the proper functionning and aging of hematopoietic stem and progenitor cells (HSPCs) in mice. Here we have found that in zebrafish development, Trim33 is essential cell-autonomously for the lifespan of the yolk sac derived primitive macrophages, as well as for the initial production of definitive (HSPC-derived) macrophages in the first niche of definitive hematopoiesis, the caudal hematopoietic tissue. Moreover, Trim33 deficiency leads to an excess production of definitive neutrophils and thrombocytes. Our data indicate that Trim33 radically conditions the differentiation ouput of aorta-derived HSPCs in all four erythro-myeloid cell types, in a niche-specific manner.