Hematopoiesis is the process by which the diverse cells of the immune system are produced.  In the classical model of the hematopoietic program, quiescent hematopoietic stem cells (HSCs) sit at the top of the hematopoietic hierarchy, with the ability to self-renew and differentiate as needed. HSCs give rise to more proliferative progenitor cells (MPPs), which possess multipotent potential but have largely or completely lost self-renewal capabilities. Even though MPPs can supply long-term hematopoietic program and function during hematopoietic recovery with minimal contribution of HSCs, not much is known about their potential significance to hematopoiesis, particularly with regards to the mechanistic understanding of their contribution.

In their new study titled "Loss of ING4 enhances hematopoietic regeneration in multipotent progenitor cells", former graduate student Dr. Georgina Anderson, her mentor Dr. Katie Kathrein, and their collaborators have identified the tumor suppressor, Inhibitor of Growth 4 (ING4), as a critical regulator of MPP homeostasis. Their study reveals that in the absence of ING4, MPPs express a transcriptional program of hematopoietic activation, yet they remain quiescent with low levels of reactive oxygen species. Functionally, ING4-deficient MPPs are capable of robust regeneration following competitive bone marrow transplantation, resulting in substantially higher blood chimerism compared to wild-type MPPs. These data suggest that ING4 deficiency promotes a poised state in MPPs, quiescent but transcriptionally primed for activation, and capable of converting the poised state into robust repopulation upon stress.