Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387621013> ?p ?o ?g. }
Showing items 1 to 78 of
78
with 100 items per page.
- W4387621013 abstract "Objective: We recently demonstrated regionalized myocardial fibrosis in patients undergoing surgical repair for Mitral Valve Prolapse. The location of fibrosis suggests a mechanically driven process wherein mechanical stress alters the phenotype of ventricular fibroblasts to promote an increase in tissue stiffness, eventually causing establishment of a fibrotic scar. We sought to better understand how mechanical stiffness affected cellular programs. Methods: We cultured primary human cardiac fibroblasts derived from the same patient on a mechanically stiff (TC Plastic, ~2GPa), as well as a mechanically soft (2kPa) substrate and then performed immunofluorescence, western blotting, RNA Seq, and ATAC Seq. Following differential analysis of omics data, we performed an integration analysis by filterinig differentially accessible chromatin to only include sites that fell within 10 kB of opened/closed chromatin. Finally, we performed a motif enrichment analysis using the online bioinformatics package Homer. Results: Immunofluorescence and western blotting revealed that cells cultured on a stiff substrate expressed canonical markers of fibroblast activation compared with soft substrates (alpha SMA, COL1A1, P<0.0001). RNA Sequencing revealed differential changes in 1615 genes in fibroblasts (FDR adjusted P<1.6*10 -6 ), several of which were subsequently validated using western blot. ATAC Seq identified 5855 regions across the genome which opened/closed in response to different mechanical environments in fibroblasts (adjusted P<0.05). Integrating these datasets revealed 803 Chromatin changes that fell within 10kb of differentially expressed genes, with AP1 and TEAD family transcription factors predicted to be master regulators of closing and opening chromatin, respectively. Proof-of-concept motif validation conducted on differentially expressed chromatin within intron 12 of the MYH10 gene demonstrated presence of a transcriptional repressor with evidence of JunD as a binding partner for this site. Conclusions: The mechanical environment plays a major role in cellular phenotype and regulates chromatin organization and expression of pro-fibrotic genes through changes in chromatin accessibility." @default.
- W4387621013 created "2023-10-14" @default.
- W4387621013 creator A5013120513 @default.
- W4387621013 creator A5030534338 @default.
- W4387621013 creator A5040510768 @default.
- W4387621013 creator A5078022639 @default.
- W4387621013 creator A5081685803 @default.
- W4387621013 creator A5088415665 @default.
- W4387621013 creator A5091472298 @default.
- W4387621013 date "2023-08-04" @default.
- W4387621013 modified "2023-10-15" @default.
- W4387621013 title "Abstract P2114: Chromatin Accessibility Governs Mechanosensitive Gene Expression In Cardiac Fibroblasts" @default.
- W4387621013 doi "https://doi.org/10.1161/res.133.suppl_1.p2114" @default.
- W4387621013 hasPublicationYear "2023" @default.
- W4387621013 type Work @default.
- W4387621013 citedByCount "0" @default.
- W4387621013 crossrefType "journal-article" @default.
- W4387621013 hasAuthorship W4387621013A5013120513 @default.
- W4387621013 hasAuthorship W4387621013A5030534338 @default.
- W4387621013 hasAuthorship W4387621013A5040510768 @default.
- W4387621013 hasAuthorship W4387621013A5078022639 @default.
- W4387621013 hasAuthorship W4387621013A5081685803 @default.
- W4387621013 hasAuthorship W4387621013A5088415665 @default.
- W4387621013 hasAuthorship W4387621013A5091472298 @default.
- W4387621013 hasConcept C101762097 @default.
- W4387621013 hasConcept C104317684 @default.
- W4387621013 hasConcept C134320426 @default.
- W4387621013 hasConcept C142724271 @default.
- W4387621013 hasConcept C150194340 @default.
- W4387621013 hasConcept C153911025 @default.
- W4387621013 hasConcept C177707886 @default.
- W4387621013 hasConcept C2776415932 @default.
- W4387621013 hasConcept C2777420927 @default.
- W4387621013 hasConcept C2780381497 @default.
- W4387621013 hasConcept C2780559512 @default.
- W4387621013 hasConcept C54355233 @default.
- W4387621013 hasConcept C71924100 @default.
- W4387621013 hasConcept C81885089 @default.
- W4387621013 hasConcept C83640560 @default.
- W4387621013 hasConcept C85265743 @default.
- W4387621013 hasConcept C86803240 @default.
- W4387621013 hasConcept C95444343 @default.
- W4387621013 hasConceptScore W4387621013C101762097 @default.
- W4387621013 hasConceptScore W4387621013C104317684 @default.
- W4387621013 hasConceptScore W4387621013C134320426 @default.
- W4387621013 hasConceptScore W4387621013C142724271 @default.
- W4387621013 hasConceptScore W4387621013C150194340 @default.
- W4387621013 hasConceptScore W4387621013C153911025 @default.
- W4387621013 hasConceptScore W4387621013C177707886 @default.
- W4387621013 hasConceptScore W4387621013C2776415932 @default.
- W4387621013 hasConceptScore W4387621013C2777420927 @default.
- W4387621013 hasConceptScore W4387621013C2780381497 @default.
- W4387621013 hasConceptScore W4387621013C2780559512 @default.
- W4387621013 hasConceptScore W4387621013C54355233 @default.
- W4387621013 hasConceptScore W4387621013C71924100 @default.
- W4387621013 hasConceptScore W4387621013C81885089 @default.
- W4387621013 hasConceptScore W4387621013C83640560 @default.
- W4387621013 hasConceptScore W4387621013C85265743 @default.
- W4387621013 hasConceptScore W4387621013C86803240 @default.
- W4387621013 hasConceptScore W4387621013C95444343 @default.
- W4387621013 hasIssue "Suppl_1" @default.
- W4387621013 hasLocation W43876210131 @default.
- W4387621013 hasOpenAccess W4387621013 @default.
- W4387621013 hasPrimaryLocation W43876210131 @default.
- W4387621013 hasRelatedWork W105663443 @default.
- W4387621013 hasRelatedWork W1552029464 @default.
- W4387621013 hasRelatedWork W1937235861 @default.
- W4387621013 hasRelatedWork W2096940779 @default.
- W4387621013 hasRelatedWork W2373672930 @default.
- W4387621013 hasRelatedWork W2551842655 @default.
- W4387621013 hasRelatedWork W2783770084 @default.
- W4387621013 hasRelatedWork W4231761662 @default.
- W4387621013 hasRelatedWork W4292230183 @default.
- W4387621013 hasRelatedWork W74981954 @default.
- W4387621013 hasVolume "133" @default.
- W4387621013 isParatext "false" @default.
- W4387621013 isRetracted "false" @default.
- W4387621013 workType "article" @default.