Identification of senescent cell subpopulations by CITE-seq analysis

IF 7.8 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology
Aging Cell Pub Date : 2024-08-14 DOI:10.1111/acel.14297
Kotb Abdelmohsen, Krystyna Mazan-Mamczarz, Rachel Munk, Dimitrios Tsitsipatis, Qiong Meng, Martina Rossi, Apala Pal, Chang Hoon Shin, Jennifer L. Martindale, Yulan Piao, Jinshui Fan, Hagai Yanai, Supriyo De, Isabel Beerman, Myriam Gorospe
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Abstract

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.

Abstract Image

Abstract Image

通过 CITE-seq 分析鉴定衰老细胞亚群。
细胞衰老是一种持续生长停滞状态,与衰老和老年相关疾病密切相关。破解衰老细胞群内部的异质性并确定治疗靶点对于缓解衰老相关病症至关重要。本研究利用质谱分析鉴定了因复制衰竭和暴露于电离辐射(IR)而衰老的细胞表面的蛋白质,并利用单细胞 CITE-seq(通过测序对转录组和表位进行细胞索引)分析进一步研究了其中的一个子集。根据细胞表面存在的蛋白质,我们确定了两种不同的红外诱导衰老细胞群:一种以高水平的 CD109 和 CD112 为特征(群 3),另一种以高水平的 CD112、CD26、CD73、HLA-ABC、CD54、CD49A 和 CD44 为特征(群 0)。我们进一步发现,0 群代表处于分裂周期 G1 期的增殖细胞和衰老细胞,细胞表面蛋白的 CITE-seq 检测可选择性地分辨出衰老组中的细胞。我们的研究突出了衰老细胞的异质性,强调了细胞表面蛋白作为区分衰老细胞程序和亚类工具的价值,为针对衰老加剧的疾病的靶向治疗策略铺平了道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Aging Cell
Aging Cell 生物-老年医学
CiteScore
14.40
自引率
2.60%
发文量
212
审稿时长
8 weeks
期刊介绍: Aging Cell, an Open Access journal, delves into fundamental aspects of aging biology. It comprehensively explores geroscience, emphasizing research on the mechanisms underlying the aging process and the connections between aging and age-related diseases.
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