Gene expression in b1-integrin wild-type and knockout mouse heart
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE14411 | GEO | 2009/01/15
SECONDARY ACCESSION(S): PRJNA114503
REPOSITORIES: GEO
Similar Datasets
Project description:Growth and expansion of ventricular chambers is essential during cardiogenesis and is achieved by proliferation of cardiac progenitors that are not fully differentiated. Disruption of this process can lead to prenatal lethality. In contrast, adult cardiomyocytes achieve growth through hypertrophy rather than hyperplasia. Although epicardial-derived signals may contribute to the proliferative process in myocytes, the factors and cell types responsible for development of the ventricular myocardial thickness are unclear. Moreover, the function of embryonic cardiac fibroblasts, derived from epicardium, and their secreted factors are largely unknown. Using a novel co-culture system, we found that embryonic cardiac fibroblasts induced proliferation of cardiomyocytes, in contrast to adult cardiac fibroblasts that promoted myocyte hypertrophy. We identified fibronectin, collagen and heparin-binding EGF-like growth factor as embryonic cardiac fibroblast-specific signals that collaboratively promoted cardiomyocyte proliferation in a paracrine fashion. b1 integrin was required for this proliferative response, and ventricular cardiomyocyte-specific deletion of b1 integrin in mice resulted in reduced myocardial proliferation and impaired ventricular compaction. These findings reveal a previously unrecognized paracrine function of embryonic cardiac fibroblasts in regulating cardiomyocyte proliferation. This SuperSeries is composed of the following subset Series: GSE14411: Gene expression in b1-integrin wild-type and knockout mouse heart GSE14412: Gene expression in mouse embyonic cardiomyocytes, fibroblasts and adult cardiac fibroblasts Refer to individual Series
2009-01-14 | E-GEOD-14414 | biostudies-arrayexpress
Project description:Growth and expansion of ventricular chambers is essential during cardiogenesis and is achieved by proliferation of cardiac progenitors that are not fully differentiated. Disruption of this process can lead to prenatal lethality. In contrast, adult cardiomyocytes achieve growth through hypertrophy rather than hyperplasia. Although epicardial-derived signals may contribute to the proliferative process in myocytes, the factors and cell types responsible for development of the ventricular myocardial thickness are unclear. Moreover, the function of embryonic cardiac fibroblasts, derived from epicardium, and their secreted factors are largely unknown. Using a novel co-culture system, we found that embryonic cardiac fibroblasts induced proliferation of cardiomyocytes, in contrast to adult cardiac fibroblasts that promoted myocyte hypertrophy. We identified fibronectin, collagen and heparin-binding EGF-like growth factor as embryonic cardiac fibroblast-specific signals that collaboratively promoted cardiomyocyte proliferation in a paracrine fashion. b1 integrin was required for this proliferative response, and ventricular cardiomyocyte-specific deletion of b1 integrin in mice resulted in reduced myocardial proliferation and impaired ventricular compaction. These findings reveal a previously unrecognized paracrine function of embryonic cardiac fibroblasts in regulating cardiomyocyte proliferation. To investigate the mechanisms responsible for the abnormalities in b1 integrin mutant mice, we performed mRNA expression microarray analyses of E12.5 wild-type and mutant hearts, well before any obvious dysfunction. RNA was isolated from wild-type and mutant hearts, and arrays were performed using Affymetrix mouse Gene 1.0 ST arrays. Analysis was performed on three biological replicates of WT and KO mouse hearts.
2009-01-14 | E-GEOD-14411 | biostudies-arrayexpress
Project description:Growth and expansion of ventricular chambers is essential during cardiogenesis and is achieved by proliferation of cardiac progenitors that are not fully differentiated. Disruption of this process can lead to prenatal lethality. In contrast, adult cardiomyocytes achieve growth through hypertrophy rather than hyperplasia. Although epicardial-derived signals may contribute to the proliferative process in myocytes, the factors and cell types responsible for development of the ventricular myocardial thickness are unclear. Moreover, the function of embryonic cardiac fibroblasts, derived from epicardium, and their secreted factors are largely unknown. Using a novel co-culture system, we found that embryonic cardiac fibroblasts induced proliferation of cardiomyocytes, in contrast to adult cardiac fibroblasts that promoted myocyte hypertrophy. We identified fibronectin, collagen and heparin-binding EGF-like growth factor as embryonic cardiac fibroblast-specific signals that collaboratively promoted cardiomyocyte proliferation in a paracrine fashion. b1 integrin was required for this proliferative response, and ventricular cardiomyocyte-specific deletion of b1 integrin in mice resulted in reduced myocardial proliferation and impaired ventricular compaction. These findings reveal a previously unrecognized paracrine function of embryonic cardiac fibroblasts in regulating cardiomyocyte proliferation. To identify candidate fibroblast-derived factors that promote myocyte proliferation, we isolated RNA from Nkx-YFP+ cardiomyocytes, embryonic cardiac fibroblasts, and adult cardiac fibroblasts and profiled mRNA expressions by microarray analyses. Arrays were performed using Affymetrix mouse Gene 1.0 ST arrays. Analysis was performed on three biological replicates of mouse embyonic cardiomyocytes, fibroblasts and adult cardiac fibroblasts.
2009-01-14 | E-GEOD-14412 | biostudies-arrayexpress
Project description:Growth and expansion of ventricular chambers is essential during cardiogenesis and is achieved by proliferation of cardiac progenitors that are not fully differentiated. Disruption of this process can lead to prenatal lethality. In contrast, adult cardiomyocytes achieve growth through hypertrophy rather than hyperplasia. Although epicardial-derived signals may contribute to the proliferative process in myocytes, the factors and cell types responsible for development of the ventricular myocardial thickness are unclear. Moreover, the function of embryonic cardiac fibroblasts, derived from epicardium, and their secreted factors are largely unknown. Using a novel co-culture system, we found that embryonic cardiac fibroblasts induced proliferation of cardiomyocytes, in contrast to adult cardiac fibroblasts that promoted myocyte hypertrophy. We identified fibronectin, collagen and heparin-binding EGF-like growth factor as embryonic cardiac fibroblast-specific signals that collaboratively promoted cardiomyocyte proliferation in a paracrine fashion. b1 integrin was required for this proliferative response, and ventricular cardiomyocyte-specific deletion of b1 integrin in mice resulted in reduced myocardial proliferation and impaired ventricular compaction. These findings reveal a previously unrecognized paracrine function of embryonic cardiac fibroblasts in regulating cardiomyocyte proliferation.
2009-01-15 | GSE14412 | GEO
Project description:Growth and expansion of ventricular chambers is essential during cardiogenesis and is achieved by proliferation of cardiac progenitors that are not fully differentiated. Disruption of this process can lead to prenatal lethality. In contrast, adult cardiomyocytes achieve growth through hypertrophy rather than hyperplasia. Although epicardial-derived signals may contribute to the proliferative process in myocytes, the factors and cell types responsible for development of the ventricular myocardial thickness are unclear. Moreover, the function of embryonic cardiac fibroblasts, derived from epicardium, and their secreted factors are largely unknown. Using a novel co-culture system, we found that embryonic cardiac fibroblasts induced proliferation of cardiomyocytes, in contrast to adult cardiac fibroblasts that promoted myocyte hypertrophy. We identified fibronectin, collagen and heparin-binding EGF-like growth factor as embryonic cardiac fibroblast-specific signals that collaboratively promoted cardiomyocyte proliferation in a paracrine fashion. b1 integrin was required for this proliferative response, and ventricular cardiomyocyte-specific deletion of b1 integrin in mice resulted in reduced myocardial proliferation and impaired ventricular compaction. These findings reveal a previously unrecognized paracrine function of embryonic cardiac fibroblasts in regulating cardiomyocyte proliferation. This SuperSeries is composed of the SubSeries listed below.
2009-01-15 | GSE14414 | GEO
Project description:Noonan syndrome (NS) is caused by mutations in RAS/ERK pathway genes, and is characterized by craniofacial, growth, cognitive and cardiac defects. NS patients with kinase-activating RAF1 alleles typically develop pathological left ventricular hypertrophy (LVH), which is reproduced in Raf1 L613V/+ knock-in mice. Here, using inducible Raf1 L613V expression, we show that LVH results from the interplay of cardiac cell types. Cardiomyocyte Raf1 L613V enhances Ca 2+ sensitivity and cardiac contractility without causing hypertrophy. Raf1 L613V expression in cardiomyocytes or activated fibroblasts exacerbates pressure overload-evoked fibrosis. Endothelial/endocardial (EC) Raf1 L613V causes cardiac hypertrophy without affecting contractility. Co-culture and neutralizing antibody experiments reveal a cytokine hierarchy (TNFα->IL6) from Raf1 L613V -expressing ECs that drives cardiomyocyte hypertrophy in vitro. Furthermore, post-natal TNFα inhibition normalizes the increased wall thickness and cardiomyocyte hypertrophy in vivo. We conclude that NS cardiomyopathy involves cardiomyocytes, ECs, and fibroblasts, TNFα/IL6 signaling components represent potential therapeutic targets, and abnormal EC signaling might contribute to other forms of LVH.
2017-05-22 | GSE95739 | GEO
Project description:During reprogramming of fibroblasts into cardiomyocyte-like cells by overexpression of transcription factors, GATA4, Hand2, Mef2C and Tbx5 (GHMT), H3K4Me2, an active histone code, shifts from fibroblast-exclusive peaks to cardiomyocyte-exclusive peaks. Important cardiac genes are gradually marked by this active histone marker. Mouse embryonic fibroblasts (MEFs) and neonatal mouse ventricular cardiomyocytes (NMVMs) represent fibroblasts and cardiomyocytes, respectively. Chromatins harvested from MEFs infected with retroviruses carrying GHMT at day 3, day 5, day 7 post-viral infection were prepared for immunoprecipitation.
2015-07-28 | E-GEOD-71392 | biostudies-arrayexpress
Project description:: The adult heart develops hypertrophy to reduce ventricular wall stress and maintain cardiac function in response to an increased workload. Although pathological hypertrophy generally progresses to heart failure, physiological hypertrophy may be cardioprotective. Cardiac-specific overexpression of the lipid-droplet protein perilipin 5 (Plin5) promotes cardiac hypertrophy, but it is unclear if this response is beneficial. We analyzed human RNA-sequencing data from the left ventricle and showed that cardiac PLIN5 expression correlates with upregulation of cardiac contraction-related processes. To investigate how elevated cardiac Plin5 levels affect cardiac contractility, we generated mice with cardiac-specific overexpression of Plin5 (MHC-Plin5 mice). These mice displayed increased left ventricular mass and cardiomyocyte size but preserved heart function. Quantitative proteomics identified sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) as a Plin5-interacting protein. Phosphorylation of phospholamban, the master regulator of SERCA2, was increased in MHC-Plin5 versus wild-type cardiomyocytes. Live imaging showed increases in intracellular Ca2+ release during contraction, Ca2+ removal during relaxation, and SERCA2 function in MHC-Plin5 versus wild-type cardiomyocytes. These results identify a role for Plin5 in improving cardiac contractility through enhanced Ca2+ signaling.
2023-01-20 | PXD035121 | Pride
Project description:In the heart, the serine carboxypeptidase cathepsin A (CatA) is distributed between lysosomes and the extracellular matrix (ECM). CatA-mediated degradation of extracellular peptides may contribute to ECM-remodeling and left ventricular (LV) dysfunction. This study aimed to evaluate the effects of CatA overexpression on LV remodeling. A proteomic analysis of the secretome of adult mouse cardiac fibroblasts upon digestion by CatA identified the extracellular antioxidant enzyme superoxide dismutase (EC-SOD) as a novel substrate of CatA (5-fold decreased abundance; p=0.0001). In vitro, cardiomyocytes and cardiac fibroblasts expressed and secreted CatA protein. EC-SOD protein was expressed and secreted only by cardiac fibroblasts. Cardiomyocyte-specific over-expression of CatA and increased activity in the LV of transgenic mice (CatA-TG) reduced EC-SOD protein levels by 43% (p<0.001). Loss of EC-SOD-mediated anti-oxidative protection resulted in accumulation of superoxide radicals (WT: 4.54±1.2 vs. CatA-TG: 8.62±2.3µmol/mg tissue/min; p=0.0012), increased inflammation, myocyte hypertrophy (WT: 19.8±1.0 vs. CatA-TG: 21.9±1.8µm; p=0.024), cellular apoptosis, and elevated mRNA expression of hypertrophy-related and pro-fibrotic marker genes, without effecting intracellular detoxifying proteins. In CatA-TG mice LV interstitial fibrosis formation was enhanced by 19% (p=0.028) and type I/type III collagen ratio was shifted towards higher abundance of collagen I fibers (p=0.026). Cardiac remodeling in CatA-TG was accompanied by increased LV weight/body weight and LV enddiastolic volume (WT: 50.8±5.8 vs. CatA-TG: 61.9±6.2 µl; p=0.018). Thus, in the heart CatA-mediated reduction of EC-SOD protein contributes to increased oxidative stress, myocyte hypertrophy, ECM remodeling and inflammation. This implicates CatA as a potential therapeutic target to prevent ventricular remodeling.
2020-07-10 | PXD019895 | Pride
Project description:Background: The protein kinase PKN2 is required for embryonic development, and PKN2 knockout mice die as a result of failure in expansion of mesoderm tissues, cardiac development and neural tube closure. In the adult, cardiomyocyte PKN2 and PKN1 (in combination) are required for cardiac adaptation to pressure-overload. The role of PKN2 in contractile cardiomyocytes during development and its role in the adult heart remain to be fully established. Methods: We used mice with cardiomyocyte-directed knockout of PKN2 or global PKN2 haploinsufficiency. Cardiac function and dimensions were assessed with high resolution episcopic microscopy, MRI, micro-CT and echocardiography. Biochemical and histological changes were assessed. Results: Cardiomyocyte-directed PKN2 knockout embryos displayed striking abnormalities in the compact myocardium, with frequent myocardial clefts and diverticula, ventricular septal defects and abnormal heart shape. The sub-Mendelian homozygous knockout survivors developed cardiac failure. RNASeq data showed upregulation of PKN2 in patients with dilated cardiomyopathy, suggesting an involvement in adult heart disease. Given the rarity of homozygous survivors with cardiomyocyte-specific deletion of PKN2, this was explored using mice with constitutive heterozygous PKN2 knockout. Cardiac hypertrophy resulting from hypertension induced by angiotensin II was reduced in haploinsufficient PKN2 mice relative to wild-type littermates, with suppression of cardiomyocyte hypertrophy and cardiac fibrosis. Conclusions: Cardiomyocyte PKN2 is essential for heart development and formation of compact myocardium, and is also required for cardiac hypertrophy in hypertension. Thus, PKN signalling may offer therapeutic options for managing congenital and adult heart diseases.
2022-06-24 | GSE206779 | GEO