TY - JOUR
T1 - Identification of senescent cell subpopulations by CITE-seq analysis
AU - Abdelmohsen, Kotb
AU - Mazan-Mamczarz, Krystyna
AU - Munk, Rachel
AU - Tsitsipatis, Dimitrios
AU - Meng, Qiong
AU - Rossi, Martina
AU - Pal, Apala
AU - Shin, Chang Hoon
AU - Martindale, Jennifer L.
AU - Piao, Yulan
AU - Fan, Jinshui
AU - Yanai, Hagai
AU - De, Supriyo
AU - Beerman, Isabel
AU - Gorospe, Myriam
N1 - Publisher Copyright:
© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
PY - 2024/1/1
Y1 - 2024/1/1
N2 - Cellular senescence, a state of persistent growth arrest, is closely associated with aging and age-related diseases. Deciphering the heterogeneity within senescent cell populations and identifying therapeutic targets are paramount for mitigating senescence-associated pathologies. In this study, proteins on the surface of cells rendered senescent by replicative exhaustion and by exposure to ionizing radiation (IR) were identified using mass spectrometry analysis, and a subset of them was further studied using single-cell CITE-seq (Cellular Indexing of Transcriptomes and Epitopes by Sequencing) analysis. Based on the presence of proteins on the cell surface, we identified two distinct IR-induced senescent cell populations: one characterized by high levels of CD109 and CD112 (cluster 3), the other characterized by high levels of CD112, CD26, CD73, HLA-ABC, CD54, CD49A, and CD44 (cluster 0). We further found that cluster 0 represented proliferating and senescent cells in the G1 phase of the division cycle, and CITE-seq detection of cell surface proteins selectively discerned those in the senescence group. Our study highlights the heterogeneity of senescent cells and underscores the value of cell surface proteins as tools for distinguishing senescent cell programs and subclasses, paving the way for targeted therapeutic strategies in disorders exacerbated by senescence.
AB - Cellular senescence, a state of persistent growth arrest, is closely associated with aging and age-related diseases. Deciphering the heterogeneity within senescent cell populations and identifying therapeutic targets are paramount for mitigating senescence-associated pathologies. In this study, proteins on the surface of cells rendered senescent by replicative exhaustion and by exposure to ionizing radiation (IR) were identified using mass spectrometry analysis, and a subset of them was further studied using single-cell CITE-seq (Cellular Indexing of Transcriptomes and Epitopes by Sequencing) analysis. Based on the presence of proteins on the cell surface, we identified two distinct IR-induced senescent cell populations: one characterized by high levels of CD109 and CD112 (cluster 3), the other characterized by high levels of CD112, CD26, CD73, HLA-ABC, CD54, CD49A, and CD44 (cluster 0). We further found that cluster 0 represented proliferating and senescent cells in the G1 phase of the division cycle, and CITE-seq detection of cell surface proteins selectively discerned those in the senescence group. Our study highlights the heterogeneity of senescent cells and underscores the value of cell surface proteins as tools for distinguishing senescent cell programs and subclasses, paving the way for targeted therapeutic strategies in disorders exacerbated by senescence.
KW - CITE-seq
KW - cell cycle
KW - proteome
KW - senescence
KW - single-cell transcriptome
KW - surface proteins
KW - surfaceome
UR - http://www.scopus.com/inward/record.url?scp=85201146881&partnerID=8YFLogxK
U2 - 10.1111/acel.14297
DO - 10.1111/acel.14297
M3 - Article
C2 - 39143693
AN - SCOPUS:85201146881
SN - 1474-9718
JO - Aging Cell
JF - Aging Cell
ER -