Abstract P3092: Transcriptomic Landscape Of The Postnatal Atrioventricular Conduction System
Bibliographic record
Abstract
The atrioventricular conduction system (AVCS) is a network of specialized cardiomyocytes responsible for coordinated spreading of electrical impulses throughout the heart to allow synchronized contractions. Specifically, it is composed of the AV node (AVN), which delays the electrical signal, and the ventricular conduction system (VCS) (i.e. His bundle, bundle branches and Purkinje fibers), which rapidly propagates the signal throughout the ventricles. Although these AVCS structures were discovered >100 years ago, its molecular constituents are not fully known. In this study, AVCS cells, making up ~0.05% of myocytes (~500 cells/heart), were isolated from early postnatal hearts (Postnatal day 1 to 4) of fluorescent reporter mice (Cntn2- Cre;Rosa26TdTomato), purified using fluorescence-activated cell sorting, and were subjected to single-cell RNA-sequencing. Unbiased cluster analysis on ~7000 AVCS cells demonstrated distinct transcriptomic profiles in the AVN, proximal-VCS (i.e. His bundle and bundle branches) and distal-VCS (i.e. Purkinje fibers). Conforming to previous studies, global conduction markers, such as Etv1 and Kcne1, were present throughout the entire AVCS, whereas a VCS-specific TF, Irx3 , was expressed only in the VCS. Additionally, Tbx3, Pcp4, Nppa and Lyz2 were enriched in the proximal, not distal, VCS. Sub-clustering analysis of AVN and proximal-VCS further identified unique molecular profiles, such as Shox2 (in compact AVN) and Rspo3 (likely in lower nodal region connecting AVN and proximal-VCS). Moreover, we uncovered a potential regulatory relationship between Irx3 and Tbx3 in the AVCS, mediating their downstream targets, Gja5 and Gja1 . In Irx3 and Tbx3 -positive proximal-VCS, Gja5 and Gja1 expressions were lower compared to only Irx3 -positive distal-VCS, whereas in only Tbx3 -positive AVN, both Gja5 and Gja1 expressions were undetected. Importantly, this regional difference was recapitulated in cultured neonatal mouse atrial and ventricular myocytes overexpressing Irx3 and/or Tbx3 . Overall, our study provides a comprehensive view of the cellular and molecular heterogeneity within the postnatal AVCS at a high-resolution and reveals novel gene regulatory mechanisms that may govern the development of the AVCS.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".