YAP/TAZ deficiency reprograms macrophage phenotype and improves infarct healing and cardiac function after myocardial infarction
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA666905 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12761300_1.fastq.gz | Fastqsanger.gz | |||
| SRR12761300_2.fastq.gz | Fastqsanger.gz | |||
| SRR12761301_1.fastq.gz | Fastqsanger.gz | |||
| SRR12761301_2.fastq.gz | Fastqsanger.gz | |||
| SRR12761302_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:Adverse cardiac remodeling after myocardial infarction (MI) causes structural and functional changes in the heart leading to heart failure. The initial pro-inflammatory response followed by an anti-inflammatory or reparative response post-MI is essential for minimizing the myocardial damage, healing, and scar formation. Bone marrow-derived macrophages (BMDMs) are recruited to the injured myocardium and essential for cardiac repair as they can adopt both pro-inflammatory (M1) or anti-inflammatory/reparative (M2) phenotypes to modulate inflammatory and reparative response, respectively. YAP and TAZ are the key mediators of the Hippo signaling pathway and essential for cardiac regeneration and repair. However, their role in macrophage polarization and post-MI inflammation, remodeling, and healing are not well established. Here, we demonstrate that expression of YAP and TAZ is increased in macrophages undergoing M1 or M2 polarization. Genetic deletion of YAP/TAZ leads to impaired M1 polarization and enhanced M2 polarization. Consistently, YAP activation/overexpression enhanced M1 and impaired M2 polarization. We show that YAP/TAZ promote M1 polarization by increasing IL6 expression, and impede M2 polarization by decreasing Arg1 expression through interaction with the HDAC3-NCoR1 repressor complex. These changes in macrophages polarization due to YAP/TAZ deletion results in reduced fibrosis, and hypertrophy and increased angiogenesis, leading to improved cardiac function after MI. Also, YAP activation augmented MI-induced cardiac fibrosis and remodeling. In summary, we identify YAP/TAZ as important regulators of macrophage-mediated pro- and anti-inflammatory responses post-MI.
2020-10-02 | GSE158889 | GEO
Project description:Adverse cardiac remodeling after myocardial infarction (MI) causes structural and functional changes in the heart leading to heart failure. The initial post-MI pro-inflammatory response followed by reparative or anti-inflammatory response is essential for minimizing the myocardial damage, healing, and scar formation. Bone marrow-derived macrophages (BMDMs) are recruited to the injured myocardium and are essential for cardiac repair as they can adopt both pro-inflammatory or reparative phenotypes to modulate inflammatory and reparative responses, respectively. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are the key mediators of the Hippo signaling pathway and are essential for cardiac regeneration and repair. However, their functions in macrophage polarization and post-MI inflammation, remodeling, and healing are not well established. Here, we demonstrate that expression of YAP and TAZ is increased in macrophages undergoing pro-inflammatory or reparative phenotype changes. Genetic deletion of YAP/TAZ leads to impaired pro-inflammatory and enhanced reparative response. Consistently, YAP activation enhanced pro-inflammatory and impaired reparative response. We show that YAP/TAZ promote pro-inflammatory response by increasing interleukin 6 (IL6) expression and impede reparative response by decreasing Arginase-I (Arg1) expression through interaction with the histone deacetylase 3 (HDAC3)-nuclear receptor corepressor 1 (NCoR1) repressor complex. These changes in macrophages polarization due to YAP/TAZ deletion results in reduced fibrosis, hypertrophy, and increased angiogenesis, leading to improved cardiac function after MI. Also, YAP activation augmented MI-induced cardiac fibrosis and remodeling. In summary, we identify YAP/TAZ as important regulators of macrophage-mediated pro-inflammatory or reparative responses post-MI.
| S-EPMC7735680 | biostudies-literature
Project description:Tissue homeostasis requires lineage fidelity of stem cells. Dysregulation of cell fate specification and differentiation leads to various diseases, yet the cellular and molecular processes remain elusive. We demonstrate that YAP/TAZ activation reprograms airway secretory cells to lose cellular identity and acquire squamous alveolar type 1 (AT1) fate in the lungs. Significantly, this cell fate conversion is mediated via distinctive transitional cell states of Damage-Associated Transient Progenitors (DATPs), recently known to emerge during injury repair, in mouse and human lungs. Further, YAP/TAZ signaling is identified to realign the amino acid metabolism by modulating mTORC1-ATF4 activity, which is integral to fate conversion of secretory cells into AT1 fate. We observed aberrant activation of the YAP/TAZ-mTORC1-ATF4 axis in the altered airway epithelium of human pulmonary fibrosis where the emergence of DATPs and A1 cells is prominent. Finally, genetic and pharmacologic inhibition of mTORC1 activity restores lineage alteration and subepithelial fibrosis driven by YAP/TAZ activation, proposing a potential therapeutic target for human fibrotic lung diseases.
2021-06-25 | GSE178829 | GEO
Project description:The Murphy Roth Large (MRL) mouse, a strain capable of regenerating right ventricular myocardium, has a high post-myocardial infarction (MI) survival rate compared with C57BL6/J (C57) mice. The biological processes responsible for this survival advantage are unknown. We compared acute post-MI gene expression in C57 and MRL hearts using microarrays and identified promising candidate biological processes underlying increased survival in the MRL. Hearts from both strains were excised at different time points before or after MI for RNA extraction and hybridization to MOE430A arrays. Baseline hearts were excised from healthy mice that had not undergone the MI procedure (day 0). Infarct tissue in this case means tissue taken from the anterior-apical region that would be the infarct region in a post-MI heart. Non-infarct covers the remainder of the LV. Post-MI hearts were excised either 1 or 5 days after MI. We had successful hybridizations for 3 replicates each of C57 day 0 infarct and non-infarct tissue (6 arrays), 4 MRL day 0 infarct and non-infarct tissue (8 arrays), 4 C57 day 1 infarct and non-infarct tissue (8 arrays), 4 MRL day 1 infarct and non-infarct tissue (8 arrays), 4 C57 day 5 infarct and non-infarct tissue (8 arrays), and 4 MRL day 5 infarct and non-infarct tissue (8 arrays).
2010-05-27 | E-GEOD-19322 | biostudies-arrayexpress
Project description:Therapeutic angiogenesis represents a promising avenue to revascularize the ischemic heart. Its limited success is partly due to our poor understanding of the cardiac stroma, specifically mural cells, and their response to ischemic injury. Here, we combine single-cell and positional transcriptomics to assess the behaviour of mural cells within the healing heart. In response to myocardial infarction, mural cells adopt an altered state closely associated with the infarct and retain a distinct lineage from fibroblasts. This response is concurrent with vascular rarefaction and reduced coverage by mural cells. Positional transcriptomics reveal that the infarcted heart is governed by regional-dependent and temporally regulated programs. While the remote zone acts as an important source of pro-angiogenic signals, the infarct zone is accentuated by chronic activation of anti-angiogenic, pro-fibrotic, and inflammatory cues. Together, our work unveils the spatiotemporal programs underlying cardiac repair and establishes an association between vascular deterioration and mural cell dysfunction.
2023-11-28 | GSE206787 | GEO
Project description:The use of cDNA microarrays has made it possible to analyze expression of thousands of genes simultaneously. We employed microarray gene expression profiling of porcine cDNA to compare myocardial gene expression in infarct core and remote myocardium at 1 week (n=3), 4 weeks (n=3), and 6 weeks (n=3) after surgically induced myocardial infarction (MI) and in sham-operated controls (n=3). More than 8,000 cDNA sequences were identified in myocardium that showed differential expression in response to MI. Different temporal and spatial patterns of gene expression were recognized in the infarct core tissue within this large set of data. Microarray gene profiling revealed candidate genes, some of them described for the first time, which elucidate changes in biological processes at different stages after MI. We evaluated temporal gene expression in a porcine model of myocardial infarction by microarray technology. Nine female pigs (Sus scrofa crossbreed Landrace x Large White) weighing 30-40 kg were subjected to experimental MI by a double-ligation of the first marginal branch of the circumflex artery. Animals were randomly sacrificed at 1 week (n=3), 4 weeks (n=3), or 6 weeks (n=3) after MI. Three paired myocardial samples from the infarct core and remote myocardium were analyzed at each time point. Myocardial samples from sham-operated animals (open-chest cardiac exposure without coronary artery ligation; n=3) were included as physiological controls.
2013-03-01 | E-GEOD-34569 | biostudies-arrayexpress
Project description:Myocardial infarction (MI) results from occlusion of blood supply to the heart muscle causing death of cardiac muscle cells. Following myocardial infarction (MI), scar formation acts to mechanically stabilise the injured heart to prevent rupture and death. While fibroblasts and macrophages are implicated in post-MI scar formation and maturation, their exact contributions to this process are poorly characterised, especially in the long-term (i.e., beyond 1-week post-MI). Here, we employ state-of-the-art spatially-targetted optical micro-proteomics (STOMP) to isolate proteomes of tissue fractions enriched for fibroblasts (sma+) and macrophages (cd68+) over a 6-week post-MI timecourse and compare them to whole-scar proteome. We illustrate dynamic, specific changes in sma- and cd68-enriched fraction protein composition over 1-6 weeks post-MI with some of these changes reflected in whole-infarct preparations. These results link specific cell populations to specific protein changes in whole infarct.
2023-10-31 | PXD034413 | Pride
Project description:The transcriptome analysis of Peri-infarct areas of infarction for sham, PT, and Pushen treatment
| PRJNA853348 | ENA
Project description:Blood milieu in acute myocardial infarction reprograms human macrophages for trauma repair
| PRJNA890635 | ENA
Project description:Endothelial cells were isolated from the infarct region (anteroapical wall distal to the coronary artery ligation site representing the infarct core and border zone) 3 days after sham or acute myocardial infarction (AMI) surgery. AMI was induced by 60 min coronary ligation followed by reperfusion. Endothelial cells were subjected to single cell RNA sequencing.
2022-06-20 | GSE198401 | GEO