Integrative transcriptomic identification of cellular senescence beyond marker limitations
Lu, J.; Guderer, I.; Alvi, T.; Olenik, M.; Dönertas, H. M.
Show abstract
Cellular senescence lacks a universal marker and varies across cell types, tissues, and stressors, complicating identification. Using SPiDER SA-{beta}-gal labeled single-cell RNA-seq from regenerating mouse muscle, we found that curated gene sets show opposing enrichment patterns in experimentally defined senescent cells, suggesting apparent concordance in prior studies may reflect circular validation. Machine learning classifiers outperformed marker-centric approaches by capturing coordinated transcriptional features largely absent from differentially expressed genes. These features traced senescence progression, positioning senescent cells at late pseudotime with reduced transcriptional entropy. Ligand-receptor analysis identified IGF signaling as a directional axis of secondary senescence from senescent to non-senescent cells. When applied to bulk RNA-seq and an independent aging dataset, the classifier detected age-associated senescence patterns while the entropy-senescence relationship held across most cell types. These findings demonstrate that transcriptome-based classification provides a robust alternative to marker-centric readouts while enabling mechanistic hypothesis generation.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Single-cell RNA sequencing reveals distinct senotypes and a quiescence-senescence continuum at the transcriptome level following chemotherapy 97%
- Cell division drives DNA methylation loss in late-replicating domains in primary human cells 97%
- Deep Phenotyping and Lifetime Trajectories Reveal Limited Effects of Longevity Regulators on the Aging Process in C57BL/6J Mice 96%
Similar papers in this journal
Similar papers in this journal
- Aging-related inflammation driven by cellular senescence enhances NAD consumption via activation of CD38+ macrophages 95%
- Enhanced Branched-Chain Amino Acid Metabolism Improves Age-related Reproductive Function 94%
- Cancer cells depend on environmental lipids for proliferation when electron acceptors are limited 94%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.