Essential Role for Trf2 in Cardiac Development and Function

Sharifi-Sanjani, M.; Hakim Shoushtari, A.; Danis, A.; Stoner, M. W.; Baust, J.; Sebastiani, A.; Bugga, P.; Manning, J. R.; Mushala, B.; Bhattarai, N.; Al Ghouleh, I.; Scott, I.

doi:10.1101/2025.09.24.677933

bioRxiv · 10.1101/2025.09.24.677933

Essential Role for Trf2 in Cardiac Development and Function

Sharifi-Sanjani, M.·Hakim Shoushtari, A.·Danis, A.·Stoner, M. W.·Baust, J.·Sebastiani, A.·Bugga, P.·Manning, J. R.·Mushala, B.·Bhattarai, N.·Al Ghouleh, I.·Scott, I.

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Abstract

Telomere Repeat-binding Factor 2 (Trf2) is essential for protecting our telomeres. While Trf2 global deletion is lethal, its role in organ-specific development, particularly in the heart, remains less understood. In this study, we investigated the role of Trf2 in cardiac development and function. Our studies reveal that cardiomyocyte (CM)-specific loss of Trf2 leads to profound defects in heart morphology, including impaired ventricular wall formation and compromised CM proliferation, concurrent with no CM telomere length attrition. Further, in vivo functional assessment and molecular analyses of CM-Trf2 deficient ventricles revealed severe cardiac dysfunction and, interestingly, altered nuclear envelope gene expression, respectively. Our work provides new insights into the essential role of Trf2 in heart development and function, and potential avenues for therapeutic intervention targeting telomere biology.

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Sharifi-Sanjani, M., Hakim Shoushtari, A., Danis, A., Stoner, M. W., Baust, J., Sebastiani, A., Bugga, P., Manning, J. R., Mushala, B., Bhattarai, N., Al Ghouleh, I., Scott, I.. 2025-09-30. Essential Role for Trf2 in Cardiac Development and Function. https://doi.org/10.1101/2025.09.24.677933

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