Impact of myeloid cell specific deletion of EGFR on cardiac Cd11b+ non-myocyte gene expression
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PROVIDER: PRJNA856688 | ENA |
REPOSITORIES: ENA
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Project description:Epidermal Growth Factor Receptor (EGFR) is a critical factor regulating numerous aspects of cell biology. Though it is widely recognized as an oncogene, EGFR has been implicated in cardiovascular health, and has been shown to have unique cell specific roles in the heart. Macrophages and other myeloid cells play key roles in normal cardiac physiology and post injury pathological outcomes. Myeloid cell EGFR has been implicated in disease, though its role in the normal or failing heart has yet to be established. Here, we crossed EGFR floxed mice with LysM Cre transgenics to specifically delete EGFR in Cd11b+ myeloid cells. We then isolated non-cardiomyocytes and subject them to Cd11b microbeads and subsequent column concentration to obtain cardiac Cd11b+ non-myocyte myeloid cells. We used samples from floxed EGFR controls, and EGFR specific myeloid knockouts. In comparisson to control, myeloid EGFR knockouts had 763 differential transcripts when consdering p adjusted less than 0.05 and log2foldchange greater than absolute value 1.5.
2023-09-21 | GSE207686 | GEO
Project description:Rationale: Neonatal mice have the capacity to regenerate their hearts in response to injury, but this potential is lost after the first week of life. The transcriptional changes that underpin mammalian cardiac regeneration have not been fully characterized at the molecular level. Objective: The objectives of our study were to determine if myocytes revert the transcriptional phenotype to a less differentiated state during regeneration and to systematically interrogate the transcriptional data to identify and validate potential regulators of this process. Methods and Results: We derived a core transcriptional signature of injury-induced cardiac myocyte regeneration in mouse by comparing global transcriptional programs in a dynamic model of in vitro and in vivo cardiac myocyte differentiation, in vitro cardiac myocyte explant model, as well as a neonatal heart resection model. The regenerating mouse heart revealed a transcriptional reversion of cardiac myocyte differentiation processes including reactivation of latent developmental programs similar to those observed during de-stabilization of a mature cardiac myocyte phenotype in the explant model. We identified potential upstream regulators of the core network, including interleukin 13 (IL13), which induced cardiac myocyte cell cycle entry and STAT6/STAT3 signaling in vitro. We demonstrate that STAT3/periostin and STAT6 signaling are critical mediators of IL13 signaling in cardiac myocytes. These downstream signaling molecules are also modulated in the regenerating mouse heart. Conclusions: Our work reveals new insights into the transcriptional regulation of mammalian cardiac regeneration and provides the founding circuitry for identifying potential regulators for stimulating heart regeneration. Comparison of transcriptional programs of primary myocardial tissues sampled from neonatal mice and murine hearts undergoing post-injury regeneration, along with in vitro ESC-differentiated cardiomyocytes
2014-12-20 | E-GEOD-64403 | biostudies-arrayexpress
Project description:Rationale: Neonatal mice have the capacity to regenerate their hearts in response to injury, but this potential is lost after the first week of life. The transcriptional changes that underpin mammalian cardiac regeneration have not been fully characterized at the molecular level. Objective: The objectives of our study were to determine if myocytes revert the transcriptional phenotype to a less differentiated state during regeneration and to systematically interrogate the transcriptional data to identify and validate potential regulators of this process. Methods and Results: We derived a core transcriptional signature of injury-induced cardiac myocyte regeneration in mouse by comparing global transcriptional programs in a dynamic model of in vitro and in vivo cardiac myocyte differentiation, in vitro cardiac myocyte explant model, as well as a neonatal heart resection model. The regenerating mouse heart revealed a transcriptional reversion of cardiac myocyte differentiation processes including reactivation of latent developmental programs similar to those observed during de-stabilization of a mature cardiac myocyte phenotype in the explant model. We identified potential upstream regulators of the core network, including interleukin 13 (IL13), which induced cardiac myocyte cell cycle entry and STAT6/STAT3 signaling in vitro. We demonstrate that STAT3/periostin and STAT6 signaling are critical mediators of IL13 signaling in cardiac myocytes. These downstream signaling molecules are also modulated in the regenerating mouse heart. Conclusions: Our work reveals new insights into the transcriptional regulation of mammalian cardiac regeneration and provides the founding circuitry for identifying potential regulators for stimulating heart regeneration.
2014-12-20 | GSE64403 | GEO
Project description:Gene expression changes in neonatal rat ventricular myocytes plated in fibronectin (2 samples) or uncoated plates (2 samples). Keywords = Hypertrophy Cardiac Myocyte Fibronectin Keywords: repeat sample
2004-08-19 | GSE1055 | GEO
Project description:We characterized single-cell transcriptional profiles of the cardiac non-myocyte cell pool in C57BL/6J mice. The cell preparation we sequenced consisted of metabolically active, nucleated non-myocyte cells from heart ventricles of female and male mice which were depleted of endothelial cells. The goals of this experiment included examining cellular diversity, identifying markers of understudied cell populations, exploring functional roles of different cell types, and characterizing sexual dimorphism in cardiac gene expression.
2017-11-21 | E-MTAB-6173 | biostudies-arrayexpress
Project description:Single Cell Transcriptome Profiling of Cardiac Non-myocyte
| PRJNA661315 | ENA
Project description:Single Cell Epigenome Profiling of Cardiac Non-myocyte
| PRJNA661319 | ENA
Project description:The mammalian heart is composed of a variety types of cells that can be roughly categorized into cardiomyocytes and non-myocytes. Instead of being bystanders of cardiac function, cardiac non-myocytes provide critical structural, mechanical and electrophysiological support to the working myocardium. However, the precise cellular identity and molecular features of the non-myocytes at single cell level remain elusive. Depiction of epigenetic landscape with transcriptomic signatures using the latest single cell multi-omics has the potential to unravel the molecular programs of cardiac non-myocytes underlying their cellular diversity. To characterize the molecular and cellular features of cardiac non-myocytes populations in the adult murine heart at single cell level. We applied single cell Assay for Transposase Aaccessible Chromatin using sequencing (scATAC-seq) in combination with high-throughput single cell RNA-seq (scRNA-seq) to map the epigenetic landscape and gene expression program of cardiac non-myocytes from adult murine heart. Through integrated dual-omics data analysis, we categorize the cardiac non-myocytes into 4 defined populations including endothelial cells, fibroblast, pericytes and immune cells with distinct chromatin accessibility patterns. Cis- and trans-regulatory factors for each cell type were identified. In particular, unbiased sub-clustering and functional annotation of the cardiac fibroblast (FB), indicated the heterogeneity and functionality of FB subtypes associated with cellular response, cytoskeleton organization and immune regulation. We further validated the expression and function of novel markers in major FB sub-populations and experimentally determined the distribution of the FB sub-populations in healthy and injured murine heart. In summary, we comprehensively characterized the non-myocyte cellular identity at the single-cell level and defined FB subpopulations by their functional states.
2021-04-21 | GSE157445 | GEO
Project description:The mammalian heart is composed of a variety types of cells that can be roughly categorized into cardiomyocytes and non-myocytes. Instead of being bystanders of cardiac function, cardiac non-myocytes provide critical structural, mechanical and electrophysiological support to the working myocardium. However, the precise cellular identity and molecular features of the non-myocytes at single cell level remain elusive. Depiction of epigenetic landscape with transcriptomic signatures using the latest single cell multi-omics has the potential to unravel the molecular programs of cardiac non-myocytes underlying their cellular diversity. To characterize the molecular and cellular features of cardiac non-myocytes populations in the adult murine heart at single cell level. We applied single cell Assay for Transposase Aaccessible Chromatin using sequencing (scATAC-seq) in combination with high-throughput single cell RNA-seq (scRNA-seq) to map the epigenetic landscape and gene expression program of cardiac non-myocytes from adult murine heart. Through integrated dual-omics data analysis, we categorize the cardiac non-myocytes into 4 defined populations including endothelial cells, fibroblast, pericytes and immune cells with distinct chromatin accessibility patterns. Cis- and trans-regulatory factors for each cell type were identified. In particular, unbiased sub-clustering and functional annotation of the cardiac fibroblast (FB), indicated the heterogeneity and functionality of FB subtypes associated with cellular response, cytoskeleton organization and immune regulation. We further validated the expression and function of novel markers in major FB sub-populations and experimentally determined the distribution of the FB sub-populations in healthy and injured murine heart. In summary, we comprehensively characterized the non-myocyte cellular identity at the single-cell level and defined FB subpopulations by their functional states.
2021-04-21 | GSE157444 | GEO
Project description:Cardiac myocyte-specific ERalpha KO mice were generated to assess the role of ERα in the heart. Female ERαHKO mice displayed a modest cardiac phenotype, but unexpectedly, an the most striking obesity phenotype developed was obesity in female ERαHKO but not male ERαHKO mice. In female ERαHKO mice we identified cardiac dysfunction, mild glucose and insulin intolerance, and reduced ERα gene expression in skeletal muscle and white adipose tissue (WAT). RNA-seq analysis was conducted on the ventricles and WAT of male and female ERαHKO mice to further elucidate the transcriptomic alterations associated with the shift in metabolic profiles in the tissues of interest.
2023-01-24 | E-MTAB-12564 | biostudies-arrayexpress