Single-cell transcriptomic analysis uncovers diverse and dynamic senescent cell populations
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) mRNA, and another in which cells expressed long noncoding RNAs and splicing was dysregulated. Finally, we obtained evidence that the proliferation status at the time of senescence initiation affected the path of senescence, as determined based on the expressed RNAs. We propose that a deeper understanding of the transcriptomes during the progression of different senescent cell phenotypes will help develop more effective interventions directed at this detrimental cell population.
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Pseudobulk RNA-seq showed that classical senescence markers (Il6, Bcl2l2, Ccnd1, Ccnd2, Cdkn1a, Lmnb1, Lbr mRNAs) were increased by HFD and reduced by ABT-737.
“The pseudobulk RNA-seq assessment also revealed that the levels of classical senescence markers, including Il6, Bcl2l2, Ccnd1, Ccnd2, Cdkn1a, Lmnb1 and Lbr mRNAs, were increased by HFD and reduced by ABT-737 (Extended Data Fig. 1j)22,23.”
From Single-cell and spatial transcriptomics map senescent vascular cells in arterial remodeling during atherosclerosis in mice (2025) · cites this paper as [23]
The Results section on senescent-cell clusters (page not provided) identifies several listed mRNAs as senescence-associated markers in WI-38 fibroblasts. It reports changes after etoposide treatment, not HFD or ABT-737, and reports decreases—not increases—in LMNB1 and LBR mRNAs. The cited paper therefore does not support the claimed pseudobulk treatment effects. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn another scRNA-seq study on WI-38, IGFBP7 overexpression with one-vs.-others comparisons was established, with log2FC = 1.7 for RS, 1.3 for IR-induced senescent cells, and 1.2 for ETO-induced senescent cells.
“The overexpression of IGFBP7, with one-vs.-others comparisons, was also established in another scRNA-seq study on WI-38, with the amount of its overexpression compared to others being particularly large (specifically, RS: log2FC = 1.7, IR-induced senescent cells: log2FC = 1.3, and ETO-induced senescent cells: log2FC = 1.2) [17].”
From Ensemble of Time-Evolving SASP Gene Sets Identifies IGFBP7 and CDKN1A as a Potential Marker Pair for Senescent Fibroblast Subpopulations Across Tissues (2026) · cites this paper as [17]
The Results section on WI-38 senescence models reports scRNA-seq analysis and lists IGFBP7 among markers upregulated in senescent cells relative to proliferating controls. It does not give the claimed one-vs.-others IGFBP7 comparisons or the RS, IR, and ETO log2FC values of 1.7, 1.3, and 1.2. Page numbers are unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredCDKN1A expression increased for 2 days following etoposide treatment but then decreased.
“CDKN1A (p21) was found to be overexpressed in WI-38 cells at PDL_50np, although it was reported that CDKN1A expression increased for 2 days following etoposide treatment but then decreased [17].”
From Ensemble of Time-Evolving SASP Gene Sets Identifies IGFBP7 and CDKN1A as a Potential Marker Pair for Senescent Fibroblast Subpopulations Across Tissues (2026) · cites this paper as [17]
The Results section ('Cell state dynamics in ETO-induced senescence initiation and progression'; page unavailable) reports that CDKN1A was induced in cluster 2 cells on Day 1 after etoposide treatment and gradually decreased at later time points. It does not establish that expression continued increasing for two days before declining, and the reported pattern is specific to that cell cluster. (LLM, conf=0.84)
Experimental — accuracy not yet measuredSERPINE2 was identified as a marker for RS, IR-induced senescence, and ETO-induced senescence in single-cell data obtained from WI-38.
“SERPINE2 was identified as a marker for RS, IR-induced senescence, and ETO-induced senescence in single-cell data obtained from WI-38 [17].”
From Ensemble of Time-Evolving SASP Gene Sets Identifies IGFBP7 and CDKN1A as a Potential Marker Pair for Senescent Fibroblast Subpopulations Across Tissues (2026) · cites this paper as [17]
CDKN1A was generally overexpressed in senescent cells induced by multiple stimuli, i.e., replicative senescence (RS), ionizing radiation (IR), and etoposide (ETO).
“It was reported that CDKN1A was generally overexpressed in senescent cells induced by multiple stimuli, i.e., replicative senescence (RS), ionizing radiation (IR), and etoposide (ETO) [17].”
From Ensemble of Time-Evolving SASP Gene Sets Identifies IGFBP7 and CDKN1A as a Potential Marker Pair for Senescent Fibroblast Subpopulations Across Tissues (2026) · cites this paper as [17]
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Mazan-Mamczarz, K., Tsitsipatis, D., Childs, B. G., Carr, A. E., Dos Santos, C. R., Anerillas, C., Romero, B., Gregg, J. M., Henry-Smith, C., Okereke, A. N., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00889-z · Cited by 37 · see citing works
Self-citationWang, J., Zhou, X., Yu, P., Yao, J., Guo, P., Xu, Q., Zhao, Y., Wang, G., Li, Q., Zhu, X., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00886-2 · Cited by 28 · see citing works
Single-cell and spatial detection of senescent cells using DeepScence
Qu, Y., Ji, B., Dong, R., Gu, L., Chan, C., Xie, J., Glass, C., Wang, X.-F., Nixon, A. B., & Ji, Z. (2025) · Cell Genomics · doi:10.1016/j.xgen.2025.101035 · Cited by 30 · see citing works
Jang, D., Shim, E., Shin, J., Kim, S., Ciotlos, S., Kim, H. J., Gil, T., Kim, Y., & Jeon, O. H. (2026) · Aging Cell · doi:10.1111/acel.70540 · Cited by 2 · see citing works
Kim, H., Kummerfeld, E., Niedernhofer, L. J., Aliferis, C., Robbins, P. D., & Wang, J. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27073012 · Cited by 1 · see citing works
- Authors
- Wechter, N., Rossi, M., Anerillas, C., Tsitsipatis, D., Piao, Y., Fan, J., Martindale, J. L., De, S., Mazan-Mamczarz, K., & Gorospe, M.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Mazan-Mamczarz, Krystyna
- Gorospe, Myriam
- ORCID
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2023-04-19
- Volume
- 15
- Issue
- 8
- Pages
- 2824-2851
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC10188353
- OpenAlex
- W4366389409
- Cited by
- 43
- References
- 19
- Citations by year
- 2026: 5 · 2025: 20 · 2024: 14 · 2023: 4
- FWCI
- 7.64
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Aging (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- cellular senescence, single-cell transcriptomics, long non-coding RNA, splicing dysregulation, cell proliferation
- MeSH terms
- Aged, Aged, 80 and over, Aging, Humans, Phenotype, Cellular Senescence, Transcriptome
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