We find that MitoQ also targets elevated mitochondrial respiration and the selective advantage of human DNMT3A-mutant HSCs, supporting species conservation.

Exploiting elevated mitochondrial membrane potential, we used long-chain alkyl-TPP molecules (ex. MitoQ) that selectively accumulate in the mitochondria. These caused reduced mitochondrial respiration, apoptosis, and ablated the competitive advantage of Dnmt3a-mutant HSCs.

Dnmt3a-mutant HSCs have DNA hypomethylation and increased expression of oxidative phosphorylation gene signatures, increased functional OXPHOS capacity, high
mitochondrial membrane potential & greater dependence on mitochondrial respiration versus wild-type HSCs.

Using a mouse model of Dnmt3a-mutant CH that our lab previously developed, we found that mutant HSCs sustain elevated mitochondrial respiration which is associated with their resistance to aging-induced changes in the bone marrow microenvironment.

Happy holidays from the Trowbridge lab! The festive games got a wee bit competitive this year 😅 Thanks James for the inspiration!

Lastly, a shout out to my co-chair Sant-Rayn Pasricha (whom I will nudge onto Bluesky!) for a lot of laughs, for keeping an at-times challenging job light and fun, & for literally sharing the spotlight with me. Wouldn't have wanted to partner with anyone else. Hope to see everyone at #ASH25!

#ASH24 badge has arrived ✅ Sant-Rayn Pasricha & I are delighted & excited to see everyone in San Diego. Getting ready for Best of ASH! During the meeting, stay tuned for posts about sessions you do not want to miss. 😎