Article
Elevated mitochondrial membrane potential is a therapeutic vulnerability in Dnmt3a-mutant clonal hematopoiesis.
Nature communications - 16 Apr 2025
Young Kira A, Hosseini Mohsen, Mistry Jayna J, Morganti Claudia, Mills Taylor S, Cai Xiurong, James Brandon T, Nye Griffin J, Fournier Natalie R, Voisin Veronique, Chegini Ali, Schimmer Aaron D, Bader Gary D, Egan Grace, Mansour Marc R, Challen Grant A, Pietras Eric M, Fisher-Wellman Kelsey H, Ito Keisuke, Chan Steven M, Trowbridge Jennifer J
Abstract excerpt
The competitive advantage of mutant hematopoietic stem and progenitor cells (HSPCs) underlies clonal hematopoiesis (CH). Drivers of CH include aging and inflammation; however, how CH-mutant cells gain a selective advantage in these contexts is an unresolved question. Using a murine model of CH (Dnmt3aR878H/+), we discover that mutant HSPCs sustain elevated mitochondrial respiration which is associated with their...
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