Evidence map›Paper›PMID 40513560›Full record

ArticleCell stem cell2025

Multiomic profiling reveals that prostaglandin E2 reverses aged muscle stem cell dysfunction, leading to increased regeneration and strength.

Yu Xin Wang, Adelaida R Palla, Andrew T V Ho, Daniel C L Robinson, Meenakshi Ravichandran, Glenn J Markov, Thach Mai, Chris Still, Akshay Balsubramani, Surag Nair and 9 more

Abstract read
In one paragraph

Article in Cell stem cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed.

  1. Review
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  7. Article
  8. Review
  9. Review
  10. Article
  11. 15-PGDH inhibition promotes muscle repair and strength recovery during GLP-1 receptor agonist-induced weight loss.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Molecular evolution of animal aging.The EMBO journal · 2026
    Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Yu Xin WangBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA 94305-5175, USA; Center for Genetic Disorders and Aging, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Adelaida R PallaBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA 94305-5175, USA.
Andrew T V HoBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA 94305-5175, USA.
Daniel C L RobinsonBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA 94305-5175, USA.
Meenakshi RavichandranBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA 94305-5175, USA.
Glenn J MarkovBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA 94305-5175, USA.
Thach MaiBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA 94305-5175, USA.
Chris StillInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA.
Akshay BalsubramaniDepartment of Genetics, Stanford University, Stanford, CA, USA; Department of Computer Science, Stanford University, Stanford, CA, USA.
Surag NairDepartment of Genetics, Stanford University, Stanford, CA, USA.
Colin A HolbrookBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA 94305-5175, USA.
Ann V YangBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA 94305-5175, USA.
Peggy E KraftBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA 94305-5175, USA.
Shiqi SuBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA 94305-5175, USA; Center for Genetic Disorders and Aging, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
David M BurnsBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA 94305-5175, USA.
Nora D YucelBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA 94305-5175, USA.
Lei S QiDepartment of Bioengineering, Stanford University, Stanford, CA, USA; Department of Chemical and Systems Biology, Stanford University, Stanford, CA, USA; ChEM-H, Stanford University, Stanford, CA, USA.
Anshul KundajeDepartment of Genetics, Stanford University, Stanford, CA, USA; Department of Computer Science, Stanford University, Stanford, CA, USA.
Helen M BlauBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA 94305-5175, USA. Electronic address: hblau@stanford.edu.

Funding

Stanford Center for Clinical and Translational Research and EducationUM1TR004921 · NCATS · STANFORD UNIVERSITY · PI MANISHA DESAI, DEAN W FELSHER · 2024 to 2026
$30.1M
Spatial Regulators of Skeletal Muscle Regeneration and DiseaseR00NS120278 · NINDS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI WANG, YU XIN · 2023 to 2025
$739k
Spatial Regulators of Skeletal Muscle Regeneration and DiseaseK99NS120278 · NINDS · STANFORD UNIVERSITY · PI WANG, YU XIN · 2020 to 2021
$177k
NCATS NIH HHS UM1 TR004921NINDS NIH HHS K99 NS120278NINDS NIH HHS R00 NS120278
6 · The paper itself

Abstract

Repair of muscle damage declines with age due to the accumulation of dysfunctional muscle stem cells (MuSCs). Here, we uncover that aged MuSCs have blunted prostaglandin E2 (PGE2)-EP4 receptor signaling, which causes precocious commitment and mitotic catastrophe. Treatment with PGE2 alters chromatin accessibility and overcomes the dysfunctional aged MuSC fate trajectory, increasing viability and triggering cell cycle re-entry. We employ neural network models to learn the complex logic of transcription factors driving the change in accessibility. After PGE2 treatment, we detect increased transcription factor binding at sites with CRE and E-box motifs and reduced binding at sites with AP1 motifs, overcoming the changes that occur with age. We find that short-term exposure of aged MuSCs to PGE2 augments their long-term regenerative capacity upon transplantation. Strikingly, PGE2 injections following myotoxin- or exercise-induced injury overcome the aged niche, leading to enhanced regenerative function of endogenous tissue-resident MuSCs and an increase in strength.

Indexed as

Cellular SenescenceDinoprostoneMuscle, SkeletalRegenerationStem CellsAnimalsMiceMice, Inbred C57BLReceptors, Prostaglandin E, EP4 SubtypeSignal TransductionDinoprostoneReceptors, Prostaglandin E, EP4 Subtypeagingepigenetic remodelinginflammagingmolecular memorymuscle stem cellsneural network analysisProstaglandin E2regenerationrejuvenationsarcopenia

Identifiers

PMID40513560
PMCPMC12935322

What Socratic holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.