通过全基因组CRISPRi筛选鉴定复制衰老和炎症衰老特征

IF 10.1 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genome Biology Pub Date : 2025-08-06 DOI:10.1186/s13059-025-03683-7

Lingling Wu, Xiang Zhu, Yanxia Liu, Dehua Zhao, Betty Chentzu Yu, Zheng Wei, Xueqiu Lin, Lei S. Qi

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引用次数: 0

摘要

衰老是慢性疾病和癌症的主要危险因素。细胞老化，特别是在成体干细胞中，为解剖衰老的分子机制提供了一个高通量的框架。我们对来自脂肪组织的人原代间充质干细胞在复制性衰老或炎症性衰老过程中进行了多次全基因组CRISPR干扰（CRISPRi）筛选。这些筛选揭示了针对每种衰老途径的不同的潜在的新型调节因子。结合我们基于微扰的功能基因组数据和405个全基因组关联研究数据集，包括50个衰老相关研究，我们发现从CRISPRi筛选中鉴定出的炎症衰老特征与多种衰老过程显著相关，这为分析和预测衰老状态和衰老相关疾病提供了新的分子特征。通过综合功能基因组学和遗传分析验证的特征可能为调节衰老过程和提高细胞治疗产品质量提供新的靶点。

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Identification of replicative aging and inflammatory aging signatures via whole-genome CRISPRi screens

Aging is a major risk factor for chronic diseases and cancer. Cellular aging, particularly in adult stem cells, offers a high-throughput framework for dissecting the molecular mechanisms of aging. We perform multiple genome-wide CRISPR interference (CRISPRi) screenings in human primary mesenchymal stem cells derived from adipose tissue during either replicative senescence or inflammation-induced senescence. These screens reveal distinct sets of potential novel regulators specific to each senescence pathway. Combining our perturbation-based functional genomic data with 405 genome-wide association study datasets, including 50 aging-related studies, we find that the inflammatory aging signatures identified from CRISPRi screenings are significantly associated with diverse aging processes, suggesting novel molecular signatures for analyzing and predicting aging status and aging-related disease. The signatures verified through comprehensive functional genomics and genetic analyses may provide new targets for modulating the aging process and enhancing the quality of cell therapy products.

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来源期刊

Genome Biology Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

21.00

自引率

3.30%

发文量

241

审稿时长

2 months

期刊介绍： Genome Biology stands as a premier platform for exceptional research across all domains of biology and biomedicine, explored through a genomic and post-genomic lens. With an impressive impact factor of 12.3 (2022),* the journal secures its position as the 3rd-ranked research journal in the Genetics and Heredity category and the 2nd-ranked research journal in the Biotechnology and Applied Microbiology category by Thomson Reuters. Notably, Genome Biology holds the distinction of being the highest-ranked open-access journal in this category. Our dedicated team of highly trained in-house Editors collaborates closely with our esteemed Editorial Board of international experts, ensuring the journal remains on the forefront of scientific advances and community standards. Regular engagement with researchers at conferences and institute visits underscores our commitment to staying abreast of the latest developments in the field.