Objectives:

1. Non-homologous end joining-mediated DNA misrepair in quiescent HSCs is associated with the acquisition of genomic rearrangements, which persist in vivo and contribute to clonal expansion of abnormal HSCs.
2. The unfolded protein response in mitochondria (UPRmt) mediates the metabolic remodeling required for HSC entry to and exit from quiescence and the loss of Sirtuin 7 leads to the dysregulation of the UPRmt and promotes HSC aging.
3. A regulator of local, but not systemic, insulin-like growth factor 1 (IGF-1) signaling has dramatic effects on HSCs and their myeloid progeny, which may have therapeutic implications clonal hematopoiesis and myeloproliferative neoplasms and their associated comorbidities.