Identification of senescent cell subpopulations by CITE-seq analysis.

IF 8 1区 医学 Q1 CELL 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

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。
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来源期刊
Aging Cell
Aging Cell Biochemistry, Genetics and Molecular Biology-Cell Biology
自引率
2.60%
发文量
212
期刊介绍: Aging Cell is an Open Access journal that focuses on the core aspects of the biology of aging, encompassing the entire spectrum of geroscience. The journal's content is dedicated to publishing research that uncovers the mechanisms behind the aging process and explores the connections between aging and various age-related diseases. This journal aims to provide a comprehensive understanding of the biological underpinnings of aging and its implications for human health. The journal is widely recognized and its content is abstracted and indexed by numerous databases and services, which facilitates its accessibility and impact in the scientific community. These include: Academic Search (EBSCO Publishing) Academic Search Alumni Edition (EBSCO Publishing) Academic Search Premier (EBSCO Publishing) Biological Science Database (ProQuest) CAS: Chemical Abstracts Service (ACS) Embase (Elsevier) InfoTrac (GALE Cengage) Ingenta Select ISI Alerting Services Journal Citation Reports/Science Edition (Clarivate Analytics) MEDLINE/PubMed (NLM) Natural Science Collection (ProQuest) PubMed Dietary Supplement Subset (NLM) Science Citation Index Expanded (Clarivate Analytics) SciTech Premium Collection (ProQuest) Web of Science (Clarivate Analytics) Being indexed in these databases ensures that the research published in Aging Cell is discoverable by researchers, clinicians, and other professionals interested in the field of aging and its associated health issues. This broad coverage helps to disseminate the journal's findings and contributes to the advancement of knowledge in geroscience.
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