Figure 6. Model of LT-HSC aging and inflammatory myeloid-bias.
Shifts in clonal heterogeneity during LT-HSC aging affects the inflammatory response of LT-HSCs. The LT-HSC compartment is comprised of unbiased and myeloid-biased LT-HSCs. With age, the clonal distribution of LT-HSCs shifts towards myeloid-biased variants which express high levels of CD61. During acute inflammatory challenges, aged myeloid-biased LT-HSCs preferentially expand, leading to increased myeloid output. Several cell-intrinsic factors, including the transcriptional regulators Klf5, Ikzf1 and Stat3 may play a role in establishing a myeloid-biased differentiation program during aging and inflammation. Extrinsic factors, including inflammatory cytokines and growth factors secreted from other cell types may also play a role.
