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Record W4394800354

Pulmonary vascular remodeling and PAH : Characterization of PW1+ pulmonary vascular progenitors and regulation by the PDGFRα pathway

2021· preprint· en· W4394800354 on OpenAlexfundno aff
Julien Solinc

Bibliographic record

Venuetheses.fr (ABES) · 2021
Typepreprint
Languageen
FieldMedicine
TopicPulmonary Hypertension Research and Treatments
Canadian institutionsnot available
FundersInstitut de Cardiométabolisme et NutritionMedical Research CouncilCanadian Institutes of Health ResearchNew South Wales GovernmentFondation pour la Recherche MédicaleNational Health and Medical Research CouncilFondation LeducqLaboratoire d'Excellence en Recherche sur le Médicament et l'Innovation ThérapeutiqueAgence Nationale de la Recherche
KeywordsProgenitor cellMedicineLungCell biologyInternal medicineBiologyStem cell
DOInot available

Abstract

fetched live from OpenAlex

L’hypertension artérielle pulmonaire (HTAP) est une maladie rare et sévère due à l’occlusion progressive des artérioles pulmonaires. Lors de cette thèse, j’ai étudié les populations de progéniteurs pulmonaires PW1+ et leur régulation par la voie PDGFRα. Chez les patients, le nombre de cellules périvasculaires PW1+/PDGFRα+/αSMA- et celui des cellules PW1+/PDGFRα+/αSMA+ dans la media et la néointima des vaisseaux pulmonaires sont augmentés, potentiellement suite à l’activation de PDGFRα. Dans un modèle murin d’hypertension pulmonaire (HP), l’hypoxie chronique (HC) induit une prolifération et une différenciation des progéniteurs PW1+ en CML, contribuant au remodelage des artérioles pulmonaires. L’inhibition de PDGFRα prévient ces phénomènes précoces sans empêcher l’établissement d’une HP à 28 jours d’HC. A l’inverse, en normoxie, l’activation constitutive de PDGFRα induit la différenciation des progéniteurs PW1+ en CML et la muscularisation des artérioles pulmonaires, ainsi qu’une HP chez les mâles après 5 semaines. In vitro, l’activation de PDGFRα entraine uniquement la prolifération des cellules PW1+/PDGFRα+/c-kit-. Pour conclure, PDGFRα régule la prolifération des progéniteurs PW1+ et leur différenciation en CML, contribuant au remodelage vasculaire lors de l’HTAP. Un 2nd projet a été initié pour caractériser par single-cell RNAseq les différentes populations progénitrices PW1+ et celles qui en dérivent. Nous avons identifié 3 clusters de progéniteurs semblant se différencier en CML d’après l’analyse de trajectoire. L’un des 3 clusters présente une bipotentialité, observée in vitro en différenciant les cellules PW1+/PDGFRα+/c-kit+ en CML et en CE.

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: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.023
GPT teacher head0.252
Teacher spread0.229 · 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 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

Citations0
Published2021
Admission routes1
Has abstractyes

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Same venuetheses.fr (ABES)Same topicPulmonary Hypertension Research and TreatmentsFrench-language works237,207