This study investigated age- and sex-associated alterations in the human heart at the single-cell level using single-nucleus combinatorial indexing (sci) ATAC- and RNA-sequencing. The researchers identified hundreds of differentially expressed genes by age and sex, revealing epigenetic signatures and variations in metabolic and immune processes across different cell types. They also compared adult and fetal ATAC-Seq profiles to identify developmental stage-specific regulatory factors and built predictive models of cell-type-specific RNA expression using ATAC-Seq profiles to link regulatory sequences to promoters. This research represents the largest single-cell analysis of cardiac aging by age and sex to date.

David F. Read, Gregory T. Booth, Riza M. Daza, Dana L. Jackson, Rula Green Gladden, Sanjay R. Sivatsan, Brent Ewing, Jennifer M. Franks, Cailyn H. Spurrell, Anne Roshella Gomes, Diana O'Day, Aishwarya A. Gogate, Beth K. Martin, Haleigh Larson, Christian Pfleger, Lea Starita, Ying Lin, Jay Shendure, Shin Lin, Cole Trapnell