Evidence map›Paper›PMID 27894125›Full record

ArticleNature2016

Intronic polyadenylation of PDGFRα in resident stem cells attenuates muscle fibrosis.

Alisa A Mueller, Cindy T van Velthoven, Kathryn D Fukumoto, Tom H Cheung, Thomas A Rando

Abstract read
In one paragraph

Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed
6.4field-weighted citation impact, top 3% of its field
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

91 citing papers in PubMed, 125 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Targeting C1q signaling in fibro-adipogenic progenitors prevents regenerative fibrosis of aged muscle.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  8. Review
  9. Article
  10. Reduced Usage ofPhenomics (Cham, Switzerland) · 2025
    Article
  11. Article
  12. Article
  13. Article
  14. PdgfrαGenes & diseases · 2025
    Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Circumvention of Topoisomerase IIMolecular pharmacology · 2024
    Article
  20. Review

31 more citing papers are in PubMed but not listed here.

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

5 authors at 1 institution in 1 country.

Alisa A MuellerPaul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, California, USA.
Cindy T van VelthovenPaul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, California, USA.
Kathryn D FukumotoPaul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, California, USA.
Tom H CheungPaul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, California, USA.
Thomas A RandoPaul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, California, USA.
Stanford University · US

Funding

Wnt signaling in muscle stem cell agingP01AG036695 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MARGARET A. GOODELL · 2011 to 2026
$29.3M
A New Muscle-Brain Axis Underlying the Cognitive Benefits of Physical ActivityR01AG047820 · NIA · PALO ALTO VETERANS INSTIT FOR RESEARCH · PI RANDO, THOMAS A., WYSS-CORAY, TONY · 2013 to 2017
$3.5M
Notch Signaling and Satellite Cell ActivationR37AG023806 · NIA · STANFORD UNIVERSITY · PI RANDO, THOMAS A. · 2010 to 2019
$2.9M
The Function and Regulation of Pax3 in Muscle Stem CellsR01AR062185 · NIAMS · PALO ALTO VETERANS INSTIT FOR RESEARCH · PI RANDO, THOMAS A. · 2011 to 2015
$1.5M
Notch Signaling and Satellite Cell ActivationR01AG023806 · NIA · STANFORD UNIVERSITY · PI RANDO, THOMAS A. · 2005 to 2009
$1.2M
Age related muscle fibrosis via PDGFRa signaling in fibroadipogenic progenitorsF30AG043235 · NIA · STANFORD UNIVERSITY · PI MUELLER, ALISA ANNE · 2012 to 2015
$125k
The Effect of Exercise on the Efficacy of Neural Innervation in the Treatment of Volumetric Muscle LossI21RX002234 · VA · VETERANS ADMIN PALO ALTO HEALTH CARE SYS · PI RANDO, THOMAS A. · 2016 to 2017
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Regulation of Muscle Fibrosis in Response to Injury and AgingI01BX002324 · VA · VETERANS ADMIN PALO ALTO HEALTH CARE SYS · PI RANDO, THOMAS A. · 2014 to 2021
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BLRD VA I01 BX002324NIAMS NIH HHS R01 AR062185NIA NIH HHS F30 AG043235NIA NIH HHS P01 AG036695NIA NIH HHS R01 AG023806NIA NIH HHS R01 AG047820NIA NIH HHS R37 AG023806RRD VA I21 RX002234
6 · The paper itself

Abstract

Platelet-derived growth factor receptor α (PDGFRα) exhibits divergent effects in skeletal muscle. At physiological levels, signalling through this receptor promotes muscle development in growing embryos and angiogenesis in regenerating adult muscle. However, both increased PDGF ligand abundance and enhanced PDGFRα pathway activity cause pathological fibrosis. This excessive collagen deposition, which is seen in aged and diseased muscle, interferes with muscle function and limits the effectiveness of gene- and cell-based therapies for muscle disorders. Although compelling evidence exists for the role of PDGFRα in fibrosis, little is known about the cells through which this pathway acts. Here we show in mice that PDGFRα signalling regulates a population of muscle-resident fibro/adipogenic progenitors (FAPs) that play a supportive role in muscle regeneration but may also cause fibrosis when aberrantly regulated. We found that FAPs produce multiple transcriptional variants of Pdgfra with different polyadenylation sites, including an intronic variant that codes for a protein isoform containing a truncated kinase domain. This variant, upregulated during regeneration, acts as a decoy to inhibit PDGF signalling and to prevent FAP over-activation. Moreover, increasing the expression of this isoform limits fibrosis in vivo in mice, suggesting both biological relevance and therapeutic potential of modulating polyadenylation patterns in stem-cell populations.

Indexed as

PolyadenylationAdipocytesAdipogenesisAnimalsFibroblastsFibrosisIntronsMaleMiceMuscle, SkeletalMuscular DiseasesProtein IsoformsReceptor, Platelet-Derived Growth Factor alphaRegenerationSignal TransductionStem CellsProtein IsoformsReceptor, Platelet-Derived Growth Factor alpha

Identifiers

PMID27894125
PMCPMC5384334
OpenAlexW2559061868

What OpenQuestion holds

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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 OpenQuestion graph.