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Expression data from SAN tissue of WT and HCN4FEA mice

ABSTRACT: HCN4 channels are the major HCN channel isoform expressed in the sinoatrial node (SAN) and play a key role in cardiac pacemaking. We have characterized the gene expression profile in the SAN of adult mice expressing cAMP-insensitive HCN4 channels (HCN4FEA mice) in comparison to WT mice. In this dataset, we include the expression data obtained from dissected mouse SAN tissue of WT and HCN4FEA mice. These data are used to show that there are no relevant compensatory up- oder down-regulated genes in the SAN of HCN4FEA mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE138086 | GEO | 2020/09/11

REPOSITORIES: GEO

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Genome-wide mRNA expression analyses revealed dysregulation of genes important for SAN function in Hcn4-CreERT2;Isl1 mutants.

Project description:Understanding factors that drive development and function of the sinoatrial node (SAN) is crucial to development of potential therapies for sinus arrhythmias, including potential generation of biological pacemakers. Here, we identify a key cell autonomous role for the LIM homeodomain transcription factor ISL1 for survival, proliferation and function of pacemaker cells throughout development. Analysis of several Isl1 mutant mouse lines, including one in which Isl1 was specifically ablated in SAN (Hcn4- CreERT2;Isl1) revealed an early requirement for Isl1 within SAN for embryonic viability. RNA-seq analyses on FACS purified SAN cells revealed dysregulation of a number of genes critical for SAN function to be downstream of ISL1 in Hcn4-CreERT2;Isl1 mutants, including transcription factors and ion channels. Our studies demonstrated that ISL1 regulated approximately one third of genes that were significantly expressed in SAN, and highlight the potential for utilization of ISL1 in combination with other SAN transcription factors for generating pacemaker cells for therapy or drug screening purposes. Results also suggest Isl1 as a candidate gene for sick sinus syndrome. RNA-seq analyses were performed on samples from Hcn4-CreERT2;Isl1 mutant and control SANs

2015-07-24 | E-GEOD-69097 | biostudies-arrayexpress

Genome-wide mRNA expression analyses revealed dysregulation of genes important for SAN function in Hcn4-CreERT2;Isl1 mutants.

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Single-cell RNA-seq achieve the transcriptome module the SAN morphogenesis and the pacemaking cell fate determinant

Project description:We analyze three (WT, Shox2-KO, Double-KO) different samples to segregate the transcriptional factors that modulate the SAN morphogenesis and the pacemaking cell fate determinants.

2020-05-20 | GSE143997 | GEO

Genome-wide chromatin-immunoprecipitation studies of purified SAN cells reveals critical direct targets of ISL1 and suggests potential co-factor families for ISL1 action in SAN cells

Project description:Understanding factors that drive development and function of the sinoatrial node (SAN) is crucial to development of potential therapies for sinus arrhythmias, including potential generation of biological pacemakers. Here, we identify a key cell autonomous role for the LIM homeodomain transcription factor ISL1 for survival, proliferation and function of pacemaker cells throughout development. Chromatin immunoprecipitation assays performed utilizing antibody to ISL1 in chromatin extracts from FACS purified SAN cells demonstrated that ISL1 directly binds genomic regions within several genes critical for normal pacemaker function, including subunits of the L-type calcium channel, Ank2, and Tbx3. Other genes implicated in abnormal heart rhythm in humans were also direct downstream targets of ISL1 in SAN cells. Our studies represent the first in vivo ChIP-seq studies for SAN cells which provide a basis for further exploration of factors critical to SAN formation and function and highlight the potential for utilization of ISL1 in combination with other SAN transcription factors for generating pacemaker cells for therapy or drug screening purposes. ISL1 ChIP-seq profiling was performed in Hcn4-H2BGFP SAN cells purified from neonatal hearts.

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Cellular Heterogeneity Analysis of the Sinoatrial Node Region Identifies Novel His-bundle-like Cell and Endothelial Progenitor Subtypes

Project description:Aims: To gain insight into heterogeneity of pacemaker and conduction cells within the sinoatrial node (SAN) and characterize the transcriptome of cardiac endothelial cells (ECs) at single-cell resolution. Methods and results: Single-cell transcriptome analysis of fluorescence activated cell sorting (FACS)-purified SAN cells and surrounding atrial cells from HCN4-GFP knockin mice at postnatal day 2 were performed. Subcluster analysis of SAN cardiomyocyte cluster identified three HCN4+ cell subtypes, including pacemaker cells (PCs), recently identified transitional cells (TCs), and a novel population of His-like conduction cells marked by His-bundle specific marker genes. We additionally refined the molecular signatures of PCs and TCs, and identified Vsnl1, Myl2 and Kcne1 as biomarkers of PCs, TCs and His-like respectively that persistently expressed in the SAN from E15.5 to adult. Furthermore, we observed three endothelial progenitor subtypes (endocardial progenitors, coronary vascular endothelial progenitors, and transitional endothelium migrated from endocardium to coronary vessels) in mouse heart and human fetal heart. These endothelial progenitor subtypes were further identified by mouse lineage tracing analysis. Conclusion: Our study provides a more comprehensive understanding of molecular and cellular signatures underlying pacemaking and conduction of the SAN, and offers new insight into lineage differentiation and diversification of cardiac ECs.

2022-08-18 | GSE182692 | GEO

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Evidence of superior and inferior sinoatrial nodes in the mammalian heart [Human]

Project description:We report the application of RNA sequencing technology for high-throughput profiling of regionally separated sinoatrial nodal tissues from human hearts. We find that both the superior and inferior regions of these sinoatrial nodal tissues (termed sSAN and iSAN, respectively) possess statistically comparable levels of cardiac ion channels, receptors, neural proteins, and transcription factors. This study provides new insights into regional molecular expression of pacemaking tissue in the right atria.

2021-04-26 | GSE149541 | GEO

MiRNAs sequence of macrophages derived exosoms in WT group and Roquin-1 san:san group.

Project description:We reported the function of Roquin-1 in the miRNA-sorting of macrophages derived exosomes. At first, we used the supernatant of 929 cells to culture the bone marrow derived macrophages (BMDM) from bone marrow cells of WT and Roquin-1 san:san mice. Then, we isolated the macrophages derived exosomes by ultracentrifugation. At last, we performed Next-generation sequencing to detect the differences of miRNA-sorting between WT and Roquin-1 macrophages derived exosomes.

2021-03-20 | GSE169215 | GEO

Genome-wide chromatin-immunoprecipitation studies of purified SAN cells reveals critical direct targets of ISL1 and suggests potential co-factor families for ISL1 action in SAN cells

Project description:Understanding factors that drive development and function of the sinoatrial node (SAN) is crucial to development of potential therapies for sinus arrhythmias, including potential generation of biological pacemakers. Here, we identify a key cell autonomous role for the LIM homeodomain transcription factor ISL1 for survival, proliferation and function of pacemaker cells throughout development. Chromatin immunoprecipitation assays performed utilizing antibody to ISL1 in chromatin extracts from FACS purified SAN cells demonstrated that ISL1 directly binds genomic regions within several genes critical for normal pacemaker function, including subunits of the L-type calcium channel, Ank2, and Tbx3. Other genes implicated in abnormal heart rhythm in humans were also direct downstream targets of ISL1 in SAN cells. Our studies represent the first in vivo ChIP-seq studies for SAN cells which provide a basis for further exploration of factors critical to SAN formation and function and highlight the potential for utilization of ISL1 in combination with other SAN transcription factors for generating pacemaker cells for therapy or drug screening purposes.

2015-07-23 | GSE68974 | GEO

Odz4 upregulates SAN-specific genes to promote differentiation into cardiac pacemaker-like cells

Project description:Cardiac arrhythmias stemming from abnormal sinoatrial node (SAN) function can lead to sudden death. Developing a biological pacemaker device for treating sick sinus syndrome (SSS) could offer a potential cure. Understanding SAN differentiation is crucial, yet its regulatory mechanism remains unclear. We reanalyzed published RNA-seq data and identified Odz4 as a SAN-specific candidate. In situ hybridization revealed Odz4 expression in the cardiac crescent and throughout the cardiac conduction system (CCS). To assess role of Odz4 in CCS differentiation, we utilized a Tet-Off inducible system for its intracellular domain (ICD). Odz4-ICD exogenously expressing embryonic bodies (EBs) exhibited an increased propensity to develop into pacemaker-like cells with enhanced automaticity and upregulated expression of SAN-specific genes. CellChat and GO analyses unveiled SAN-specific enrichment of ligand-receptor sets, especially Ptn-Ncl, and extracellular matrix components in the Odz4-ICD exogenously expressing group. Our findings underscore the significance of Odz4 in SAN development and offer fresh insights into biological pacemaker establishment

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