MétaCan
Menu
Back to cohort
Record W4295037663 · doi:10.1101/2022.09.09.507274

Apelin Stimulation of the Perivascular MuSC Niche Enhances Endogenous Repair in Muscular Dystrophy

2022· preprint· en· W4295037663 on OpenAlexafffund
Emméran Le Moal, Yuguo Liu, Jasmin Collerette-Tremblay, Simon Dumontier, Joël Boutin, Junio Dort, Zakaria Orfi, Joris Michaud, Hugo Giguère, Alexandre Desroches, Kien Trân, François Vézina, Sonia Bédard, Catherine Raynaud, Frédéric Balg, Philippe Sarret, Michelle S. Scott, Jérôme N. Feige, Jean‐Bernard Denault, Nicolas A. Dumont, Éric Marsault, Mannix Auger‐Messier, C. Florian Bentzinger

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2022
Typepreprint
Languageen
FieldMedicine
TopicApelin-related biomedical research
Canadian institutionsCentre Hospitalier Universitaire Sainte-JustineUniversité de MontréalCentre Hospitalier Universitaire de SherbrookeUniversité de Sherbrooke
FundersFonds de Recherche du Québec - SantéCanadian Institutes of Health ResearchStem Cell NetworkUniversité de SherbrookeNatural Sciences and Engineering Research Council of CanadaHeart and Stroke Foundation of Canada
KeywordsMuscular dystrophySkeletal muscleDuchenne muscular dystrophyStem cellRegeneration (biology)BiologyPhenocopyMyocyteStimulationCell biologyCancer researchEndocrinologyGeneticsPhenotype

Abstract

fetched live from OpenAlex

Abstract Impaired skeletal muscle stem cell (MuSC) function has long been suspected to contribute to the pathogenesis of muscular dystrophy (MD). Here we describe that defects in the endothelial cell (EC) compartment of the perivascular stem cell niche in three different types of MD are associated with inefficient mobilization of MuSCs following tissue damage. Using chemoinformatic analysis, we identified the 13 amino acid form of the peptidic hormone apelin (AP-13) as a candidate for systemic stimulation of skeletal muscle ECs. In dystrophic mice, administration of AP-13 generates a pro-myogenic EC-rich niche that supports MuSC function and markedly improves tissue regeneration, muscle strength, and physical performance. Moreover, we demonstrate that EC specific knockout of the AP-13 receptor leads to regenerative defects that phenocopy major pathological features of MD. Altogether, we provide in vivo proof-of-concept that enhancing endogenous repair by targeting the perivascular niche is a viable therapeutic avenue for MD and characterize AP-13 as a novel drug candidate for systemic treatment of stem cell dysfunction.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Research integrity
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.758
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.002
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0010.003
Insufficient payload (model declined to judge)0.0010.000

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 head0.024
GPT teacher head0.262
Teacher spread0.237 · 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 teacher head, not a consensus.

Study designBench or experimental
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

Citations1
Published2022
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicApelin-related biomedical researchFrench-language works237,207