Impact of Dietary Protein Content on Hematopoietic Stem Cell Proteostasis

Abstract

Hematopoietic stem cells (HSCs) regenerate blood and immune cells throughout life. Recent discoveries have revealed that HSC fitness and longevity depend on precise regulation of protein homeostasis (proteostasis). HSCs depend on low rates of protein synthesis to prevent the biogenesis of misfolded and unfolded proteins, and modest changes in protein synthesis rates can severely impair HSC fitness and self-renewal by disrupting proteostasis. However, the factors that influence protein synthesis regulation in HSCs are largely unknown. Essential amino acids required for protein biogenesis cannot be synthesized and must be acquired dietarily. This raises the possibility that dietary protein content influences stem cell proteostasis. The central goal of this project is to determine if low and high dietary protein content alters HSC proteostasis and regenerative potential in vivo. These studies could reveal how dietary interventions influence stem cell fitness and longevity by shaping the proteostasis network.