Integrated Chromatin Accessibility and Transcriptomic Profiles Across Replicative Senescence Stages in Human Colonic Fibroblasts

Abstract

Cellular senescence is accompanied by widespread chromatin and transcriptional remodeling, but datasets that capture these changes across intermediate stages of replicative senescence remain limited. Here, we present an integrated bulk RNA-seq and ATAC-seq resource generated from primary human colonic fibroblasts spanning three replicative states: early-passage young cells, intermediate pre-senescent cells, and late-passage senescent cells. This serial design enables not only endpoint comparison between young and senescent cells but also stepwise evaluation of molecular changes during senescence progression. Bulk RNA-seq profiles captured transcriptome-wide alterations across the three states, while ATAC-seq defined corresponding changes in chromatin accessibility. By integrating promoter-associated accessibility with gene expression, we generated a gene-level multi-omic resource for evaluating concordant and discordant chromatin-transcription relationships across senescence transitions. The dataset also supports downstream analyses including pathway enrichment and transcription factor activity inference. Together, this dataset provides a useful resource for studying chromatin accessibility, transcriptional regulation, and their coupling during the progression of replicative senescence in human colonic fibroblasts.