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Endothelial RNF20 Suppresses Endothelial-to-Mesenchymal Transition and Safeguards Physiological Angiocrine Signaling to Prevent Congenital Heart Disease

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE246928 | GEO | 2025/09/24

REPOSITORIES: GEO

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Endothelial RNF20 Suppresses Endothelial-to-Mesenchymal Transition and Safeguards Physiological Angiocrine Signaling to Prevent Congenital Heart Disease

Project description:Heart morphogenesis and function rely on intricate communication among distinct cardiac cell types. How their co-development and crosstalk are coordinated is largely unexplored. Our study unveils the functions of the histone H2B ubiquitin (H2Bub1) ligase RNF20 in second heart field development and cardiac endothelial cells. We demonstrate that RNF20 promotes Nrg1 expression through a RNF20-H2Bub1-dependent mechanism and restrains TGF-β signaling by influencing RNA polymerase II pause release at TGF-β target genes in endothelial cells. While heightened TGF-β signaling following RNF20 loss results endothelial-to-mesenchymal transition (EndMT), both impaired Nrg1 signaling and elevated TGF-β activity contribute to abnormal cardiomyocyte proliferation and contractility. Importantly, RNF20 expression is significantly reduced in cardiac endothelial cells from congenital heart disease patients showing a positive correlation with oxygen saturation and a negative correlation with key components and downstream effectors of TGF-β signaling. In summary, our work identifies a crucial role for RNF20 in safeguarding endothelial identity and physiological angiocrine signaling, thereby ensuring proper heart development and function.

2025-09-24 | GSE246904 | GEO

Endothelial RNF20 Suppresses Endothelial-to-Mesenchymal Transition and Safeguards Physiological Angiocrine Signaling to Prevent Congenital Heart Disease [polyAbulkRNA_seq_Cd31_pos_EC_Rnf20_het]

2025-09-24 | GSE246926 | GEO

Endothelial RNF20 Suppresses Endothelial-to-Mesenchymal Transition and Safeguards Physiological Angiocrine Signaling to Prevent Congenital Heart Disease [Heart_scRNAseq_E11_5_Cdh5cre_Rnf20KO]

2025-09-24 | GSE246905 | GEO

Endothelial RNF20 Suppresses Endothelial-to-Mesenchymal Transition and Safeguards Physiological Angiocrine Signaling to Prevent Congenital Heart Disease [Day07_EC_Cd31po_polyARNA-Seq]

2025-09-24 | GSE288314 | GEO

Endothelial RNF20 Suppresses Endothelial-to-Mesenchymal Transition and Safeguards Physiological Angiocrine Signaling to Prevent Congenital Heart Disease [Bulk_polyA RNA-seq]

Project description:Heart development and function rely on intricate communication among distinct cardiac cell types. How their co-development and crosstalk are coordinated is largely unexplored. Our study unveils novel functions of the histone H2B ubiquitin (H2Bub1) ligase RNF20 in second heart field development and cardiac endothelial cells, essential for proper cardiac morphogenesis and function. We demonstrate that RNF20-H2Bub1-dependent reduction in Nrg1 expression, coupled with heightened TGF-β signaling due to RNF20's role in inducing RNA polymerase II pausing at TGF-β targets, drives increased endothelial-to-mesenchymal transition (EndMT), abnormal cardiomyocyte proliferation, and irregular contractility upon endothelial RNF20 loss. Importantly, RNF20 expression is significantly reduced in cardiac endothelial cells from congenital heart disease patients showing a positive correlation with oxygen saturation and a negative correlation with key components and downstream effectors of TGF-β signaling. In summary, our work identifies a novel role of RNF20 in controlling signaling inputs that safeguard physiological angiocrine signaling ensuring proper cardiac morphogenesis and function.

2025-09-24 | GSE305562 | GEO

Endothelial RNF20 Suppresses Endothelial-to-Mesenchymal Transition and Safeguards Physiological Angiocrine Signaling to Prevent Congenital Heart Disease

Project description:Endothelial RNF20 Suppresses Endothelial-to-Mesenchymal Transition and Safeguards Physiological Angiocrine Signaling to Prevent Congenital Heart Disease

| PRJNA1035110 | ENA

Endothelial RNF20 Suppresses Endothelial-to-Mesenchymal Transition and Safeguards Physiological Angiocrine Signaling to Prevent Congenital Heart Disease

Project description:Endothelial RNF20 Suppresses Endothelial-to-Mesenchymal Transition and Safeguards Physiological Angiocrine Signaling to Prevent Congenital Heart Disease

| PRJNA1035081 | ENA

Endothelial RNF20 Suppresses Endothelial-to-Mesenchymal Transition and Safeguards Physiological Angiocrine Signaling to Prevent Congenital Heart Disease [Heart_scRNAseq_E11_5_Cdh5cre_Rnf20KO]

Project description:Endothelial RNF20 Suppresses Endothelial-to-Mesenchymal Transition and Safeguards Physiological Angiocrine Signaling to Prevent Congenital Heart Disease [Heart_scRNAseq_E11_5_Cdh5cre_Rnf20KO]

| PRJNA1035082 | ENA

Endothelial RNF20 Suppresses Endothelial-to-Mesenchymal Transition and Safeguards Physiological Angiocrine Signaling to Prevent Congenital Heart Disease [polyAbulkRNA_seq_Cd31_pos_EC_Rnf20_het]

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Endothelial RNF20 Suppresses Endothelial-to-Mesenchymal Transition and Safeguards Physiological Angiocrine Signaling to Prevent Congenital Heart Disease [Day07_EC_Cd31po_polyARNA-Seq]

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