Microglial clonal dynamics and the impact of clonal hematopoiesis in autologously transplanted rhesus macaques - PubMed
3 hours ago
- #microglia replacement
- #clonal hematopoiesis
- #HSPC transplantation
- Under steady-state conditions in mice, yolk sac-derived microglia show minimal turnover from hematopoietic stem/progenitor cells (HSPCs).
- In rhesus macaques receiving barcoded or CRISPR-edited (TET2-mutant) HSPC transplants, fewer than 2% of microglia were derived from HSPCs many years post-transplant.
- Clonal hematopoiesis (CH) did not enhance microglia replacement, with rare HSPC-derived cells showing a macrophage-like gene expression profile.
- The findings demonstrate limited long-term microglia replacement from adult HSPCs, contrasting with prior human studies, and inform strategies for CNS-targeted HSPC gene therapies.