Abstract 15203: Single Cell Transcriptional Analysis Implicates <i>Acta2</i> Positive Pericytes in Arterial Muscularization and Imbalance in Bmp and Angpt Signaling During Development of Pulmonary Arterial Hypertension
Bibliographic record
Abstract
Introduction: Pulmonary arterial hypertension (PAH) is a lethal disease characterized by marked vascular remodeling, inflammation and increased pulmonary vascular resistance. Pericytes normally play a key role in maintaining microvascular homeostasis; however, they can also contribute to increased muscularization of distal arterioles in PAH by giving rise to smooth cells (SMCs). Methods: Sprague-Dawley rats were injected with 20mg/kg SU subcutaneously and exposed to 3 weeks of chronic hypoxia (CH, 10% O2). Right ventricular systolic pressure (RVSP) was measured at baseline, 1, 3, 5, and 8-weeks, then lungs were explanted, digested, and dissociated into single cells which were sequenced using the 10x genomics platform. Results: RVSP was significantly elevated at 1 week after SU (47mmHg) reaching a plateau of >100 mmHg by 5 weeks. Dimensionality reduction of the scRNAseq data was performed using Uniform Manifold Approximation and Projection (UMAP) analysis resulting in 24 lung clusters and sub-clustering of stomal populations yielded seven clusters. In addition to fibroblasts, SMC/myofibroblasts and mesothelial cells, we identified 2 distinct pericyte clusters both expressing canonical pericyte markers such as Pdgfrb and Csgp4 ( Ng2 ) and differentiated by presence or absence of Acta2 . Acta2 + pericytes exhibited high expression of contractile markers (i.e., Myh11 and Tagln ), consistent with partial SMC differentiation, and underwent a substantial (>3-fold) expansion during PAH development. The Acta2 + pericytes also exhibited profound downregulation in the endothelial protective gene, Bmpr2 , with a reciprocal upregulation of Rbpms2 , a gene which inhibits BMP signaling. Similarly, reciprocal reduction in Angpt1 , an agonist of the endothelial Tie2 receptor and an increase in expression the partial Tie2 antagonist, Angpt2 , thereby favoring EC activation and inflammation. Conclusion: These results suggest expansion of Acta2 + pericytes in PAH may contribute to distal arteriolar muscularization as well as an imbalance in BMP/TGFß and ANGPT1/2 signaling, promoting EC apoptosis, activation, and inflammation in the SU/CH model.
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 imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
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 source (direct Gemma or distilled Codex), 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".