Identification of senescent cell subpopulations by CITE-seq analysis

Deciphering the heterogeneity within senescent cell populations and identifying therapeutic targets are paramount for mitigating senescence-related pathologies. In this study, proteins on the surface of senescent cells were identified using mass spectrometry, and a subset of them was used for single-cell CITE-seq (Cellular Indexing of Transcriptomes and Epitopes by Sequencing) analysis.

Among seven clusters of senescent cells identified, cluster 1 was characterized by high levels of CD109 and CD112 on the plasma membrane, and cluster 2 by high levels of CD44, CD73, CD49a, and CD54 on the plasma membrane. The transcriptomes of cluster 1 revealed cells in which translation was reduced, proteolysis was increased, and SASP factors including IL1B, GDF15, CCL13, and CCL2 were expressed. The transcriptomes of cluster 2 revealed cells that expressed a different subset of SASP factors such as VEGFA, IL13, IL15, FGF2, and FGF7, as well as extracellular matrix remodeling factors.