Evidence map›Paper›PMID 40044687›Full record

ArticleNature communications2025

Single-nuclei sequencing of skeletal muscle reveals subsynaptic-specific transcripts involved in neuromuscular junction maintenance.

Alexander S Ham, Shuo Lin, Alice Tse, Marco Thürkauf, Timothy J McGowan, Lena Jörin, Filippo Oliveri, Markus A Rüegg

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing 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

33 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. A who's who of cell types in skeletal muscle.Communications biology · 2026
    Review
  6. Article
  7. Review
  8. Muscle fibre denervation in ageing.Clinical science (London, England : 1979) · 2026
    Review
  9. Article
  10. Article
  11. Article
  12. Junctions in Jeopardy: the neuromuscular junction is a selective pathological target in Charcot-Marie-Tooth disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026
    Review
  13. Review
  14. Article
  15. Article
  16. Article
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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

8 authors.

Alexander S HamBiozentrum, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0009-0001-6947-615X
Shuo LinBiozentrum, University of Basel, Basel, Switzerland.
Alice TseBiozentrum, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0009-0009-5092-2752
Marco ThürkaufBiozentrum, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0001-8164-872X
Timothy J McGowanBiozentrum, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0009-0005-6757-2040
Lena JörinBiozentrum, University of Basel, Basel, Switzerland.
Filippo OliveriBiozentrum, University of Basel, Basel, Switzerland.
Markus A RüeggBiozentrum, University of Basel, Basel, Switzerland. markus-a.ruegg@unibas.ch.ORCID http://orcid.org/0000-0002-4974-9384

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The neuromuscular junction (NMJ) is the synapse formed between motor neurons and skeletal muscle fibers. Its stability relies on the continued expression of genes in a subset of myonuclei, called NMJ myonuclei. Here, we use single-nuclei RNA-sequencing (snRNA-seq) to identify numerous NMJ-specific transcripts. To elucidate how the NMJ transcriptome is regulated, we also performed snRNA-seq on sciatic nerve transected, botulinum toxin injected, and Musk knockout muscles. The data show that NMJ gene expression is not only driven by agrin-Lrp4/MuSK signaling but is also affected by electrical activity and trophic factors other than agrin. By selecting the three NMJ genes Etv4, Lrtm1, and Pdzrn4, we further characterize novel contributors to NMJ stability and function. AAV-mediated overexpression shows that Etv4 is sufficient to upregulate the expression of -50% of the NMJ genes in non-synaptic myonuclei, while AAV-CRISPR/Cas9-mediated muscle-specific knockout of Pdzrn4 induces NMJ fragmentation. Further investigation of Pdzrn4 revealed that it localizes to the Golgi apparatus and interacts with MuSK protein. Collectively, our data provide a rich resource of NMJ transcripts, highlight the importance of ETS transcription factors at the NMJ, and suggest a novel pathway for NMJ post-translational modifications.

Indexed as

Muscle, SkeletalNeuromuscular JunctionAgrinAnimalsMaleMiceMice, Inbred C57BLMice, KnockoutMotor NeuronsReceptor Protein-Tyrosine KinasesReceptors, CholinergicSequence Analysis, RNASingle-Cell AnalysisTranscriptomeAgrinMuSK protein, mouseReceptor Protein-Tyrosine KinasesReceptors, Cholinergic

Identifiers

PMID40044687
PMCPMC11882927

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Registered trials

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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.