The molecular regulation of human hematopoietic stem cell (HSC) self-renewal and maintenance is of substantial interest, but limitations in experimental systems and interspecies variation have constrained our knowledge of this process. To better discern in vivoHSC function in humans, we have studied a rare genetic disorder due to MECOMhaploinsufficiency that is characterized by neonatal aplastic anemia with an early-onset absence of HSCs in vivo.