Partial reprogramming reveals lineage-specific uncoupling of rejuvenation, function, and recoverability in human cells

Partial reprogramming of human aortic endothelial cells rapidly restores identity, preserves reduced DNA methylation age, and markedly improves vascular function after Sendai-OSKM withdrawal.

• Why it matters: Therapeutic partial reprogramming must balance rejuvenation with recovery of lineage identity and function, yet it is unclear whether this balance differs across cell lineages.
• What they did: Primary human fibroblasts, cytotoxic T cells, and aortic endothelial cells were driven through reversible, traceable intermediate states using Sendai-OSKM, then recovery was followed after factor withdrawal; multiome and knockdown were used to test progression dependencies.
• The result: Recovery patterns diverged by lineage: endothelial cells recovered identity quickly and improved vascular function, while fibroblasts and T cells showed lineage-specific limits; TOX was a shared progression dependency but downstream programs were largely lineage-specific.

AI summary of the abstract · may contain errors · not medical advice · read the paper.