Analysis of Somatic Mutations in Senescent Cells Using Single-Cell Whole-Genome Sequencing

• DOI: 10.59368/agingbio.20230005
• Publication Date: 2023-06-29T15:59:37Z
• Authors: Xiao Dong; John M. Sedivy; Jan Vijg; Lei Zhang; Marco De Cecco; Moonsook Lee; Xiaoxiao Hao; Alexander Y. Maslov; Cristina Montagna; Judith Campisi
• Keywords: 0301 basic medicine; 03 medical and health sciences; Article; 3. Good health

Somatic mutations accumulate in multiple organs and tissues during aging are a known cause of cancer. Cellular senescence is possible functional decline aging, yet also acts as an anticancer mechanism vivo. Here, we compared somatic mutation burden between early passage deeply senescent human fibroblasts using single-cell whole-genome sequencing. The results show that single-nucleotide variants (SNVs) small insertions deletions (INDELs) increased cells by about twofold but have the same mutational signature cells. increase SNVs INDELs can be explained replication errors due to number cell divisions likely undergone. By contrast, stark aneuploidies was observed cells, with half all affected none analyzed. These indicate large chromosomal events rather than base substitutions or could mechanistically linked cellular senescence.