Evidence map›Paper›PMID 37823262›Full record

ArticleCirculation research2023

Single-Nuclei RNA-Sequencing of the Gastrocnemius Muscle in Peripheral Artery Disease.

Caroline G Pass, Victoria Palzkill, Jianna Tan, Kyoungrae Kim, Trace Thome, Qingping Yang, Brian Fazzone, Scott T Robinson, Kerri A O'Malley, Feng Yue and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Circulation research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
8.9field-weighted citation impact, top 1% 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

25 citing papers in PubMed, 28 citations in OpenAlex.

  1. A who's who of cell types in skeletal muscle.Communications biology · 2026
    Review
  2. CD4Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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  20. Vascular adhesion molecule 1JVS-vascular science · 2025
    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

13 authors at 1 institution in 1 country.

Caroline G PassDepartment of Applied Physiology and Kinesiology (C.G.P., V.P., J.T., K.K., T.T., Q.Y., T.E.R.), The University of Florida, Gainesville.
Victoria PalzkillDepartment of Applied Physiology and Kinesiology (C.G.P., V.P., J.T., K.K., T.T., Q.Y., T.E.R.), The University of Florida, Gainesville.ORCID 0000-0001-9382-169X
Jianna TanDepartment of Applied Physiology and Kinesiology (C.G.P., V.P., J.T., K.K., T.T., Q.Y., T.E.R.), The University of Florida, Gainesville.ORCID 0009-0001-6836-6899
Kyoungrae KimDepartment of Applied Physiology and Kinesiology (C.G.P., V.P., J.T., K.K., T.T., Q.Y., T.E.R.), The University of Florida, Gainesville.ORCID 0000-0001-9513-6469
Trace ThomeDepartment of Applied Physiology and Kinesiology (C.G.P., V.P., J.T., K.K., T.T., Q.Y., T.E.R.), The University of Florida, Gainesville.ORCID 0000-0003-4823-8547
Qingping YangDepartment of Applied Physiology and Kinesiology (C.G.P., V.P., J.T., K.K., T.T., Q.Y., T.E.R.), The University of Florida, Gainesville.ORCID 0000-0002-6261-7861
Brian FazzoneDepartment of Surgery, Division of Vascular Surgery and Endovascular Therapy (B.F., S.T.R., K.A.O., S.T.S., S.A.B.), The University of Florida, Gainesville.
Scott T RobinsonDepartment of Surgery, Division of Vascular Surgery and Endovascular Therapy (B.F., S.T.R., K.A.O., S.T.S., S.A.B.), The University of Florida, Gainesville.
Kerri A O'MalleyDepartment of Surgery, Division of Vascular Surgery and Endovascular Therapy (B.F., S.T.R., K.A.O., S.T.S., S.A.B.), The University of Florida, Gainesville.
Feng YueDepartment of Animal Sciences (F.Y.), The University of Florida, Gainesville.
Salvatore T ScaliDepartment of Surgery, Division of Vascular Surgery and Endovascular Therapy (B.F., S.T.R., K.A.O., S.T.S., S.A.B.), The University of Florida, Gainesville.ORCID 0000-0002-8128-3203
Scott A BerceliDepartment of Surgery, Division of Vascular Surgery and Endovascular Therapy (B.F., S.T.R., K.A.O., S.T.S., S.A.B.), The University of Florida, Gainesville.ORCID 0000-0003-2257-0111
Terence E RyanDepartment of Applied Physiology and Kinesiology (C.G.P., V.P., J.T., K.K., T.T., Q.Y., T.E.R.), The University of Florida, Gainesville.ORCID 0000-0003-0780-029X
University of Florida · US

Funding

Molecular mechanisms regulating peripheral arterial disease pathobiology in chronic kidney diseaseR01HL149704 · NHLBI · UNIVERSITY OF FLORIDA · PI Terence E Ryan · 2020 to 2026
$3.6M
Chronic aryl hydrocarbon receptor activation and skeletal myopathy in chronic kidney diseaseF31DK128920 · NIDDK · UNIVERSITY OF FLORIDA · PI THOME, TRACE · 2021 to 2023
$122k
NHLBI NIH HHS R01 HL149704NIDDK NIH HHS F31 DK128920
6 · The paper itself

Abstract

backgroundLower extremity peripheral artery disease (PAD) is a growing epidemic with limited effective treatment options. Here, we provide a single-nuclei atlas of PAD limb muscle to facilitate a better understanding of the composition of cells and transcriptional differences that comprise the diseased limb muscle.

methodsWe obtained gastrocnemius muscle specimens from 20 patients with PAD and 12 non-PAD controls. Nuclei were isolated and single-nuclei RNA-sequencing was performed. The composition of nuclei was characterized by iterative clustering via principal component analysis, differential expression analysis, and the use of known marker genes. Bioinformatics analysis was performed to determine differences in gene expression between PAD and non-PAD nuclei, as well as subsequent analysis of intercellular signaling networks. Additional histological analyses of muscle specimens accompany the single-nuclei RNA-sequencing atlas.

resultsSingle-nuclei RNA-sequencing analysis indicated a fiber type shift with patients with PAD having fewer type I (slow/oxidative) and more type II (fast/glycolytic) myonuclei compared with non-PAD, which was confirmed using immunostaining of muscle specimens. Myonuclei from PAD displayed global upregulation of genes involved in stress response, autophagy, hypoxia, and atrophy. Subclustering of myonuclei also identified populations that were unique to PAD muscle characterized by metabolic dysregulation. PAD muscles also displayed unique transcriptional profiles and increased diversity of transcriptomes in muscle stem cells, regenerating myonuclei, and fibro-adipogenic progenitor cells. Analysis of intercellular communication networks revealed fibro-adipogenic progenitors as a major signaling hub in PAD muscle, as well as deficiencies in angiogenic and bone morphogenetic protein signaling which may contribute to poor limb function in PAD.

conclusionsThis reference single-nuclei RNA-sequencing atlas provides a comprehensive analysis of the cell composition, transcriptional signature, and intercellular communication pathways that are altered in the PAD condition.

Indexed as

Muscle, SkeletalPeripheral Arterial DiseaseHumansLower ExtremityRNARNAischemialower extremityperipheral arterial diseaseperipheral vascular diseasestranscriptome

Identifiers

PMID37823262
PMCPMC10599805
OpenAlexW4387563489

What OpenQuestion holds

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Read underepoch 390

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.