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Record W3207744830 · doi:10.1016/j.cmet.2021.10.001

Human skeletal muscle CD90+ fibro-adipogenic progenitors are associated with muscle degeneration in type 2 diabetic patients

2021· article· en· W3207744830 on OpenAlexaff
Jean Farup, Jesper Just, Frank Vincenzo de Paoli, Lin Lin, Jonas Jensen, Tine Borum Billeskov, Inés Sánchez-Román, Cagla Cömert, Andreas Buch Møller, Luca Madaro, Elena Groppa, Rikard G. Fred, Ulla Kampmann, Lars Christian Gormsen, Steen B. Pedersen, Peter Bross, Tinna Stevnsner, Nikolaj Eldrup, Tune H. Pers, Fábio Rossi, Prem Puri, Niels Jessen

Bibliographic record

VenueCell Metabolism · 2021
Typearticle
Languageen
FieldMedicine
TopicAdipose Tissue and Metabolism
Canadian institutionsUniversity of British Columbia
FundersNational Institute of Arthritis and Musculoskeletal and Skin DiseasesSteno Diabetes Center AarhusA.P. Møller og Hustru Chastine Mc-Kinney Møllers Fond til almene FormaalDanmarks Frie ForskningsfondNovo Nordisk FondenRiisfort FondenAarhus UniversitetNovo NordiskNational Institutes of HealthH. Lundbeck A/SLundbeckfondenToyota Foundation
KeywordsSkeletal muscleAdipogenesisEndocrinologyInternal medicineProgenitor cellMetforminExtracellular matrixBiologyFibrosisPlatelet-derived growth factor receptorGrowth factorCancer researchCell biologyMedicineStem cellDiabetes mellitusAdipose tissueReceptor

Abstract

fetched live from OpenAlex

Type 2 diabetes mellitus (T2DM) is associated with impaired skeletal muscle function and degeneration of the skeletal muscles. However, the mechanisms underlying the degeneration are not well described in human skeletal muscle. Here we show that skeletal muscle of T2DM patients exhibit degenerative remodeling of the extracellular matrix that is associated with a selective increase of a subpopulation of fibro-adipogenic progenitors (FAPs) marked by expression of THY1 (CD90)—the FAP CD90+ . We identify platelet-derived growth factor (PDGF) as a key FAP regulator, as it promotes proliferation and collagen production at the expense of adipogenesis. FAPs CD90+ display a PDGF-mimetic phenotype, with high proliferative activity, clonogenicity, and production of extracellular matrix. FAP CD90+ proliferation was reduced by in vitro treatment with metformin. Furthermore, metformin treatment reduced FAP content in T2DM patients. These data identify a PDGF-driven conversion of a subpopulation of FAPs as a key event in the fibrosis development in T2DM muscle.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.013
GPT teacher head0.237
Teacher spread0.224 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations135
Published2021
Admission routes1
Has abstractyes

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