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Record W4280567845 · doi:10.21203/rs.3.rs-1647065/v1

Single-cell transcriptomics reveals diversity during heart valve epithelial-to-mesenchymal transitions

2022· preprint· en· W4280567845 on OpenAlexafffund
Jeremy Lotto, Rebecca Cullum, Sibyl Drissler, Martin Arostegui, Victoria C. Garside, Bettina M. Fuglerud, Avinash Thakur, T. Michael Underhill, Pamela A. Hoodless

Bibliographic record

VenueResearch Square · 2022
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer-related molecular mechanisms research
Canadian institutionsTerry Fox Research InstituteUniversity of British Columbia
FundersBritish Columbia Knowledge Development FundNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health Research
KeywordsMesenchymal stem cellDiversity (politics)TranscriptomeCellCell biologyBiologyGeneGene expressionGeneticsPolitical science

Abstract

fetched live from OpenAlex

Abstract The epithelial-to-mesenchymal transition (EMT) is a process critical for wound healing, fibrosis, and cancer metastasis, but is also essential for atrioventricular valve formation, where distinct EMTs of endocardium (EndMT) and epicardium (EpiMT) generate mesenchyme. To track these processes, we have analyzed over 50,000 murine single-cell transcriptomes from embryonic day (E)7.75 cardiac crescent to E12.5 atrioventricular canals. We detail mesenchymal and endocardial bifurcation during EndMT, identify a unique, Hic1-expressing epicardial population during EpiMT, and reveal epithelial-mesenchymal plasticity (EMP) during both processes. Single-cell and histological analysis of Sox9-deficient valves show the accumulation of cells exhibiting EMP. Lastly, we deconvolve the signaling pathways active during the initiation and progression of EndMT and EpiMT. Overall, these data are the first to reveal mechanisms of emergence of mesenchyme from endocardium or epicardium at single-cell resolution and will serve as an atlas of EMT initiation and progression with broad implications in regenerative medicine and cancer biology.

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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.002

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)0.0010.000

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 head0.042
GPT teacher head0.332
Teacher spread0.290 · 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

Citations2
Published2022
Admission routes2
Has abstractyes

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