Ensemble of Time-Evolving SASP Gene Sets Identifies IGFBP7 and CDKN1A as a Potential Marker Pair for Senescent Fibroblast Subpopulations Across Tissues
Year: 2026
Type: article
Abstract: The senescence-associated secretory phenotype (SASP) is a hallmark of senescent cells and plays a critical role in the development and progression of various age-related diseases, including cancer, cardiovascular disorders, and neurodegenerative diseases. In this study, we characterize SASP heterogeneity using single-cell RNA sequencing (scRNA-seq) data, focusing on the transcriptional signatures associated with elevated expression of individual SASP genes in mature senescent cells, as well as time-dependent variation in SASP expression across the early and mature senescent states in the WI-38 human lung fibroblast cell line. We generated multiple gene sets, each representing the transcriptional landscape linked to high expression of a specific SASP gene, and integrated them into an ensemble that reflects the temporal dynamics of SASP gene expression. Applying SASP scores derived from this ensemble of gene sets (SASP scores/EGS) to publicly available scRNA-seq datasets from human lung, skin, and eye tissues enabled the identification of senescent fibroblasts and revealed IGFBP7 as a consistently upregulated marker in p21+ or p16+ fibroblasts across diverse human tissues. Our framework supports improved detection of both early and mature fibroblast replicative senescent cells, offering valuable insights into aging and age-related disease research.
DOI: 10.3390/ijms27073012
Institutions: University of Minnesota, Masonic Cancer Center
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
Awards: G3840417921, G9000134543
OpenAlex ID: W7140452661