Identification of senescent cell subpopulations by CITE-seq analysis

Area of Science:

• Cellular and Molecular Biology
• Immunology
• Gerontology

Background:

• Cellular senescence is a key factor in aging and age-related diseases.
• Understanding senescent cell heterogeneity is crucial for developing effective therapies.
• Identifying specific markers for senescent cells is a significant challenge.

Purpose of the Study:

• To investigate the heterogeneity of senescent cell populations.
• To identify cell surface proteins that distinguish different types of senescent cells.
• To explore potential therapeutic targets for senescence-associated pathologies.

Main Methods:

• Mass spectrometry was used to identify surface proteins on senescent cells induced by replicative exhaustion and ionizing radiation (IR).
• Single-cell CITE-seq (Cellular Indexing of Transcriptomes and Epitopes by Sequencing) was employed for detailed analysis of cell surface protein expression.
• Bioinformatic analysis was performed to cluster and characterize distinct senescent cell populations based on protein markers.

Main Results:

• Two distinct IR-induced senescent cell populations were identified based on cell surface protein profiles.
• Cluster 3 senescent cells exhibited high levels of CD109 and CD112.
• Cluster 0 senescent cells showed high expression of CD112, CD26, CD73, HLA-ABC, CD54, CD49A, and CD44, representing proliferating and G1-phase senescent cells.

Conclusions:

• Cell surface proteins are valuable markers for distinguishing senescent cell heterogeneity and subclasses.
• CITE-seq effectively differentiates senescent cells within mixed populations.
• This research provides a foundation for developing targeted therapies against senescence-related disorders.