ABS 079: Assessing the role of chromatin regulator HIRA in a stem cell’s response to DNA damage

Sakshyat Chhetry ¹ , Ian Baranyk ¹ , Rouven Arnold ² , Peter Adams ² , Melissa Harris ¹

¹ Department of Biology, University of Alabama at Birmingham
² Sanford Burnham Prebys Medical Discovery Institute

Van Wickle (2025) Volume 1, ABS 079

Introduction: Hair graying is one of the first visible signs of aging, with its prevalence and intensity increasing substantially with age. Hair graying has been linked to a loss or dysfunction of melanocyte stem cell (McSC) populations, which give rise to pigment producing melanocytes. Understanding the biological mechanisms of hair graying can not only help develop interventions to reverse the process but can also broaden our understanding of stem cell mechanisms and tissue aging. HIRA is a protein which has been implicated in restarting transcription post DNA damage. At the same time, loss of HIRA has also been found to accelerate hair graying, with conditional knockout (KO) of HIRA in mice showing increased graying compared to wildtype (WT) counterparts. With this in mind, we aimed to assess whether decreased transcriptional restart is sufficient to explain the increased graying phenotype seen in HIRA KO mice. HIRA KO and WT mice samples were exposed to ionizing radiation to illicit DNA damage. The lower back of the mice was depilated to challenge McSC population and portions of the back skin were harvested after a week. Tissues were assessed for total McSCs and ectopically pigmented McSCs (EPMs), a trait characteristic of premature differentiation in response to ionizing radiation. The data indicated a significant decrease in overall EPMs in KO compared to WT, while the McSC population remained consistent between genotypes. This suggests that HIRA plays a vital role in forming EPMs, with transcriptional restart possibly contributing to this process.