Discovery and manipulation of transcription factors stem cell rejuvenation in aged bone-marrow
During aging, blood stem cells lose their capacity to renew and shift towards inflammatory states. Approaches that rejuvenate this population could provide new treatments for aging-associated disease. Transcription factors, master regulators of gene expression, offer a potential route to restore “youthful” cellular states. There are two challenges with identifying rejuvenating transcription factors: difficulty in defining a “youthful” state and selecting the correct factors to test for rejuvenation. Dr. Gootenberg will use two synergistic approaches to overcome these challenges. First, he will develop a “RNA clock” of aging by sequencing RNA from young and old patient blood stem cells. Second, he will profile the diversity of all transcription factors in the genome, the TFome, for potential rejuvenating factors. By screening the TFome for rejuvenation effects with RNA clocks, this can lead to understanding the biology of blood stem cell aging and identifying new potential treatments to reverse stem cell aging.