Overcoming Intrinsic Barriers in Myofibroblasts Permits Efficient Cardiac Reprogramming After Infarction.

MEOX1 upregulation is identified as the principal intrinsic barrier to efficient cardiac reprogramming of post–myocardial infarction myofibroblasts into induced cardiomyocytes.

• Why it matters: After MI, injury-activated myofibroblasts arise from quiescent fibroblasts and drive pathological fibrosis, but it was unclear whether this activated state intrinsically resists conversion to iCMs.
• What they did: The authors purified PDGFRα+ fibroblasts, used Postn lineage tracing to compare quiescent versus injury-activated myofibroblasts, profiled them by scRNA-seq, and ran a targeted shRNA screen against 9 myofibroblast-enriched TFs.
• The result: MEOX1 knockdown markedly enhanced reprogramming in mouse and human myofibroblasts, including GATA4-free combinations, and dual-recombinase lineage tracing showed highly efficient in vivo MF-to-iCM conversion with reduced fibrosis and improved cardiac function after MI.

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