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Unveiling the cell-type-specific landscape of cellular senescence through single-cell transcriptomics using SenePy

Author

Listed:
  • Mark A. Sanborn

    (College of Medicine
    University of Illinois Chicago)

  • Xinge Wang

    (College of Medicine
    University of Illinois Chicago
    College of Engineering and College of Medicine)

  • Shang Gao

    (College of Medicine
    University of Illinois Chicago
    College of Engineering and College of Medicine)

  • Yang Dai

    (University of Illinois Chicago
    College of Engineering and College of Medicine)

  • Jalees Rehman

    (College of Medicine
    University of Illinois Chicago
    College of Engineering and College of Medicine
    University of Illinois Cancer Center)

Abstract

Senescent cells accumulate in most tissues with organismal aging, exposure to stressors, or disease progression. It is challenging to identify senescent cells because cellular senescence signatures and phenotypes vary widely across distinct cell types and tissues. Here we developed an analytical algorithm that defines cell-type-specific and universal signatures of cellular senescence across a wide range of cell types and tissues. We utilize 72 mouse and 64 human weighted single-cell transcriptomic signatures of cellular senescence to create the SenePy scoring platform. SenePy signatures better recapitulate in vivo cellular senescence than signatures derived from in vitro senescence studies. We use SenePy to map the kinetics of senescent cell accumulation in healthy aging as well as multiple disease contexts, including tumorigenesis, inflammation, and myocardial infarction. SenePy characterizes cell-type-specific in vivo cellular senescence and could lead to the identification of genes that serve as mediators of cellular senescence and disease progression.

Suggested Citation

  • Mark A. Sanborn & Xinge Wang & Shang Gao & Yang Dai & Jalees Rehman, 2025. "Unveiling the cell-type-specific landscape of cellular senescence through single-cell transcriptomics using SenePy," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57047-7
    DOI: 10.1038/s41467-025-57047-7
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    1. Soyoung Lee & Yong Yu & Jakob Trimpert & Fahad Benthani & Mario Mairhofer & Paulina Richter-Pechanska & Emanuel Wyler & Dimitri Belenki & Sabine Kaltenbrunner & Maria Pammer & Lea Kausche & Theresa C., 2021. "Virus-induced senescence is a driver and therapeutic target in COVID-19," Nature, Nature, vol. 599(7884), pages 283-289, November.
    2. Sonya A. MacParland & Jeff C. Liu & Xue-Zhong Ma & Brendan T. Innes & Agata M. Bartczak & Blair K. Gage & Justin Manuel & Nicholas Khuu & Juan Echeverri & Ivan Linares & Rahul Gupta & Michael L. Cheng, 2018. "Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations," Nature Communications, Nature, vol. 9(1), pages 1-21, December.
    3. Kenji Kamimoto & Blerta Stringa & Christy M. Hoffmann & Kunal Jindal & Lilianna Solnica-Krezel & Samantha A. Morris, 2023. "Dissecting cell identity via network inference and in silico gene perturbation," Nature, Nature, vol. 614(7949), pages 742-751, February.
    4. Darren J. Baker & Bennett G. Childs & Matej Durik & Melinde E. Wijers & Cynthia J. Sieben & Jian Zhong & Rachel A. Saltness & Karthik B. Jeganathan & Grace Casaclang Verzosa & Abdulmohammad Pezeshki &, 2016. "Naturally occurring p16Ink4a-positive cells shorten healthy lifespan," Nature, Nature, vol. 530(7589), pages 184-189, February.
    5. Johannes C. Melms & Jana Biermann & Huachao Huang & Yiping Wang & Ajay Nair & Somnath Tagore & Igor Katsyv & André F. Rendeiro & Amit Dipak Amin & Denis Schapiro & Chris J. Frangieh & Adrienne M. Luom, 2021. "Author Correction: A molecular single-cell lung atlas of lethal COVID-19," Nature, Nature, vol. 598(7882), pages 2-2, October.
    6. Xiaoping Han & Ziming Zhou & Lijiang Fei & Huiyu Sun & Renying Wang & Yao Chen & Haide Chen & Jingjing Wang & Huanna Tang & Wenhao Ge & Yincong Zhou & Fang Ye & Mengmeng Jiang & Junqing Wu & Yanyu Xia, 2020. "Construction of a human cell landscape at single-cell level," Nature, Nature, vol. 581(7808), pages 303-309, May.
    7. Jan M. van Deursen, 2014. "The role of senescent cells in ageing," Nature, Nature, vol. 509(7501), pages 439-446, May.
    8. Johannes C. Melms & Jana Biermann & Huachao Huang & Yiping Wang & Ajay Nair & Somnath Tagore & Igor Katsyv & André F. Rendeiro & Amit Dipak Amin & Denis Schapiro & Chris J. Frangieh & Adrienne M. Luom, 2021. "A molecular single-cell lung atlas of lethal COVID-19," Nature, Nature, vol. 595(7865), pages 114-119, July.
    9. Yi Zhou & Yijing Su & Shiying Li & Benjamin C. Kennedy & Daniel Y. Zhang & Allison M. Bond & Yusha Sun & Fadi Jacob & Lu Lu & Peng Hu & Angela N. Viaene & Ingo Helbig & Sudha K. Kessler & Timothy Luca, 2022. "Molecular landscapes of human hippocampal immature neurons across lifespan," Nature, Nature, vol. 607(7919), pages 527-533, July.
    10. Alexandre Prieur & Emilie Besnard & Amélie Babled & Jean-Marc Lemaitre, 2011. "p53 and p16INK4A independent induction of senescence by chromatin-dependent alteration of S-phase progression," Nature Communications, Nature, vol. 2(1), pages 1-10, September.
    Full references (including those not matched with items on IDEAS)

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