Induction of PU.1 by TNF. HSCs express relatively low amounts of PU.1 protein. Inflammatory pathways induce the expression of TNF, which directly activates SPI1 via the canonical NF-κB pathway. High PU.1 concentration then activates a large group of myeloid genes and promotes differentiation to mature myeloid lineages such as macrophages. TNF-R, TNF receptor.