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Record W2804183509 · doi:10.15252/embj.201798133

Interplay of cell–cell contacts and RhoA/MRTF‐A signaling regulates cardiomyocyte identity

2018· article· en· W2804183509 on OpenAlexfundno aff
Tatjana Dorn, Jessica Kornherr, Elvira Immacolata Parrotta, Dorota Zawada, Harold Ayetey, Gianluca Santamaria, Laura Iop, Elisa Mastantuono, Daniel Sinnecker, Alexander Goedel, Ralf J. Dirschinger, Ilaria My, Svenja Laue, Tarik Bozoglu, Christian Baarlink, Tilman Ziegler, Elisabeth Graf, Rabea Hinkel, Giovanni Cuda, Stefan Kääb, Andrew A. Grace, Robert Grosse, Thomas Meitinger, Austin Smith, Karl‐Ludwig Laugwitz, Alessandra Moretti

Bibliographic record

VenueThe EMBO Journal · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCongenital heart defects research
Canadian institutionsnot available
FundersEuropean Research CouncilWellcomeMedical Research CouncilDeutsche ForschungsgemeinschaftMedical Research Council CanadaWellcome Trust
KeywordsBiologyCell biologyRHOACell fate determinationAdipogenesisProgenitor cellActin cytoskeletonCellular differentiationCellTranscription factorSignal transductionActinCytoskeletonStem cellGeneticsGeneMesenchymal stem cell

Abstract

fetched live from OpenAlex

Abstract Cell–cell and cell–matrix interactions guide organ development and homeostasis by controlling lineage specification and maintenance, but the underlying molecular principles are largely unknown. Here, we show that in human developing cardiomyocytes cell–cell contacts at the intercalated disk connect to remodeling of the actin cytoskeleton by regulating the RhoA‐ROCK signaling to maintain an active MRTF/SRF transcriptional program essential for cardiomyocyte identity. Genetic perturbation of this mechanosensory pathway activates an ectopic fat gene program during cardiomyocyte differentiation, which ultimately primes the cells to switch to the brown/beige adipocyte lineage in response to adipogenesis‐inducing signals. We also demonstrate by in vivo fate mapping and clonal analysis of cardiac progenitors that cardiac fat and a subset of cardiac muscle arise from a common precursor expressing Isl1 and Wt1 during heart development, suggesting related mechanisms of determination between the two lineages.

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 score0.001
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 head0.010
GPT teacher head0.291
Teacher spread0.280 · 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

Citations84
Published2018
Admission routes1
Has abstractyes

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Same venueThe EMBO JournalSame topicCongenital heart defects researchFrench-language works237,207