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Updated: Aug 30, 2025

Assessing Stem Cell DNA Integrity for Cardiac Cell Therapy
Published on: January 25, 2019
Somatic mutations in single human cardiomyocytes reveal age-associated DNA damage and widespread oxidative
Sangita Choudhury1,2,3, August Yue Huang4,5,6, Junho Kim4,5,6,7
1Division of Genetics and Genomics, Manton Center for Orphan Disease, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA. Sangita.choudhury@childrens.harvard.edu.
Abstract:
The accumulation of somatic DNA mutations over time is a hallmark of aging in many dividing and nondividing cells but has not been studied in postmitotic human cardiomyocytes. Using single-cell whole-genome sequencing, we identified and characterized the landscape of somatic single-nucleotide variants (sSNVs) in 56 single cardiomyocytes from 12 individuals (aged from 0.4 to 82 years). Cardiomyocyte sSNVs accumulate with age at rates that are faster than in many dividing cell types and nondividing neurons. Cardiomyocyte sSNVs show distinctive mutational signatures that implicate failed nucleotide excision repair and base excision repair of oxidative DNA damage, and defective mismatch repair. Since age-accumulated sSNVs create many damaging mutations that disrupt gene functions, polyploidization in cardiomyocytes may provide a mechanism of genetic compensation to minimize the complete knockout of essential genes during aging. Age-related accumulation of cardiac mutations provides a paradigm to understand the influence of aging on cardiac dysfunction.
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