Bnip3lb Regulated Mitophagy Maintains the Embryonic Pool of Hematopoietic Stem Cells By Protecting Them from ROS Induced Apoptosis

We have previously shown that Reactive Oxygen Species (ROS) promote Hematopoietic Stem and Progenitor Cell (HSPC) specification in the dorsal aorta, however, in the adult marrow it is established that HSPCs must maintain low levels of ROS to protect the stem cell pool against excessive cycling, differentiation, loss of stemness and apoptosis. We aim to elucidate the developmental timing and the mechanism by which HSCs transition from their initial dependence on ROS, to their precise regulation of it in the adult marrow. Since adult HSPCs regulate ROS by maintaining high levels of mitophagy, a process in which damaged mitochondria, which disproportionately generate ROS, are removed from the cell and recycled, we sought to define the initiation, regulation and impact of mitophagy in embryonic HSPC development.