Previously, megakaryocyte (Meg)-biased MPP2 and granulocyte/macrophage (G/M)-biased MPP3 were identified and characterized as novel myeloid-biased MPP subsets. They are functionally distinct from the lymphoid-primed MPP4 and are geared towards the preferential production of myeloid cells with low contribution to the lymphoid lineages. While being much smaller compartments than MPP4 at steady-state, MPP2 and MPP3 are transiently expanded in regenerative conditions and are essential for rebuilding the myeloid lineage.
Blood production skews towards myeloid lineage upon aging and myeloid malignancies with expanded MPP2 and MPP3. Production of G/M or Meg increases while lymphoid and erythroid (E) production decreases, resulting in higher risk of infection, stroke, heart attack, anemia, etc. in the elderly and various complications in myeloid leukemia patients. Therefore, our ultimate goal is to modulate this skewed lineage output to rebalance blood production.