Presented at ASH 2024, this study explores the critical role of Platelet Factor 4 (PF4) in regulating hematopoietic stem cell (HSC) aging. HSCs are essential for lifelong blood cell production, but their function declines with age, leading to immune dysfunction and an increased risk of hematologic malignancies.
Researchers found that PF4 levels decline with age in both mice and humans, leading to compromised HSC function. Aged mice exhibited megakaryocyte defects, increased myeloid bias, and DNA damage features of accelerated HSC aging. However, PF4 supplementation reversed these aging effects, restoring HSC quiescence, reducing DNA damage, and improving reconstitution potential.
Mechanistic analysis identified CXCR3 and LDLR as key receptors mediating PF4’s effects on HSC metabolism. Blocking these receptors eliminated the anti-aging benefits of PF4, suggesting a novel regulatory pathway. Importantly, human HSCs also responded to PF4, highlighting its potential therapeutic relevance.
A special thanks to all the researchers and collaborators for their dedication to advancing our understanding of HSC aging and rejuvenation.
Read more: https://lnkd.in/eJpycVds
