生物
转录因子
电池类型
调节器
免疫系统
细胞
免疫学
计算生物学
遗传学
基因
作者
Alok K. Maity,Xue Hu,Tianyu Zhu,Andrew E. Teschendorff
出处
期刊:Nature Aging
日期:2022-06-06
卷期号:2 (6): 548-561
被引量:19
标识
DOI:10.1038/s43587-022-00233-9
摘要
Transcription factors (TFs) control cell identity and function. How their activity is altered during healthy aging is critical for an improved understanding of aging and disease risk, yet relatively little is known about such changes at cell-type resolution. Here we present and validate a TF activity estimation method for single cells from the hematopoietic system that is based on TF regulons, and apply it to a mouse single-cell RNA-sequencing atlas, to infer age-associated differentiation activity changes in the immune cells of different organs. This revealed an age-associated signature of macrophage dedifferentiation, which is shared across tissue types, and aggravated in tumor-associated macrophages. By extending the analysis to all major cell types, we reveal cell-type and tissue-type-independent age-associated alterations to regulatory factors controlling antigen processing, inflammation, collagen processing and circadian rhythm, that are implicated in age-related diseases. Finally, our study highlights the limitations of using TF expression to infer age-associated changes, underscoring the need to use regulatory activity inference methods.
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