Figure 4. Unfolded protein responses promote HSC function during homeostasis and in response to stress.

A) Induction of the UPR^Mito supports HSC quiescence and prevents myeloid skewing. B) The UPR^ER is induced under homeostatic and severe levels of stress. Activation of the Ire1 and Perk branches of the UPR^ER promote HSC survival during homeostasis whereas activation of Perk can also induce apoptosis during severe stress to uphold the integrity of the HSC pool. Activation of Ire1 and Perk support survival and recovery of HSCs after transplantation and Ire1 promotes reconstitution capacity.