Schematic model of the mechanism of Tak1 protection of HSPC survival. Two distinct populations of HSPCs exist in BM hematopoietic tissue based on their response to TNF-α/Fas-induced death signaling. TNF-α/Fas, acting through RIP-1, stimulates necroptosis in 30% to 40% of HSPCs, whereas (an) unknown factor(s) induce(s) caspase-8–dependent type I or II apoptosis in the remaining HSPCs. Tak1-mediated survival signaling, stimulated by proinflammatory cytokines, prevents both types of cell death.