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Regulatory landscape of human stem cell-derived sinoatrial node-like pacemaker cells and ventricle-like cells

ABSTRACT: Regulatory landscape of human stem cell-derived sinoatrial node-like pacemaker cells and ventricle-like cells

PROVIDER: PRJNA609115 | ENA |

REPOSITORIES: ENA

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Mouse sinoatrial node transcriptome

Project description:RNA Sequencing of Mouse Sinoatrial Node Reveals an Upstream Regulatory Role for Islet-1 in Cardiac Pacemaker Cells Rationale: Treatment of sinus node disease with regenerative or cell-based therapies will require a detailed understanding of gene regulatory networks in cardiac pacemaker cells (PCs). Objective: To characterize the transcriptome of PCs using RNA sequencing, and to identify transcriptional networks responsible for PC gene expression. Methods and Results: We used laser capture micro-dissection (LCM) on a sinus node reporter mouse line to isolate RNA from PCs for RNA sequencing (RNA-Seq). Differential expression and network analysis identified novel SAN-enriched genes, and predicted that the transcription factor Islet-1 (Isl1) is active in developing pacemaker cells. RNA-Seq on SAN tissue lacking Isl1 established that Isl1 is an important transcriptional regulator within the developing SAN. Conclusions: (1) The PC transcriptome diverges sharply from other cardiomyocytes; (2) Isl1 is a positive transcriptional regulator of the PC gene expression program. There are 25 RNA-Sequencing Samples

2015-02-06 | E-GEOD-65658 | biostudies-arrayexpress

Mouse sinoatrial node transcriptome

2015-02-06 | GSE65658 | GEO

Porcine sinoatrial node extracellular matrix

Project description:comparison of pooled decellularized porcine left ventricle (LV) or sinoatrial node (SAN) extracellular matrix digested with either trypsin or elastase

2017-04-25 | MSV000081000 | MassIVE

Hippo signaling pathway maintains sinoatrial node homeostasis

Project description:The sinoatrial node (SAN) functions as pacemaker of the heart to initiate and drive rhythmic heartbeats. The Hippo signaling pathway is a fundamental pathway for heart development and regeneration. Although abnormalities of Hippo pathway are associated with cardiac arrhythmias in human patients, yet its role in the SAN is unknown. We found that Lats1/2 inactivation caused severe sinoatrial node dysfunction (SND; sick sinus syndrome). Compared to the controls, Lats1/2 CKO mutants exhibited dysregulated calcium handling and increased fibrosis in the sinoatrial node, indicating Lats1/2 function through both cell-autonomous and non-cell-autonomous mechanisms. Notably, the Lats1/2 CKO phenotype was rescued by genetic deletion of Yap and Taz in the CCS, and these rescued mice had normal sinus rhythm and reduced fibrosis of the sinoatrial node, indicating that Lats1/2 function through Yap and Taz. CUT&Tag sequencing data showed that Yap regulates genes critical for calcium homeostasis such as Ryr2 and genes encoding paracrine factors important in intercellular communication and fibrosis induction such as Tgf-β1 and Tgf-β3. Consistently, Lats1/2 CKO mutants had decreased Ryr2 expression and increased Tgf-β1 and Tgf-β3 expression compared with control mice. We reveal for the first time that the canonical Hippo-Yap pathway has a pivotal role in functional homeostasis of the sinoatrial node.

2022-11-29 | GSE202641 | GEO

Regulatory landscape of human stem cell-derived sinoatrial node-like pacemaker cells and ventricle-like cells

Project description:ATAC-seq revealed multiple pacemaker cell-specific accessible regions in the genome of pacemaker-like cells

2020-10-23 | GSE146044 | GEO

Comparative Gene Expression During Sinoatrial Node and Atrial Development

Project description:To determine pathways activated during sinoatrial node morphogenesis we conducted bulk RNA sequencing on functionally validated tissue preps of embryonic sinoatrial node and atria.

2023-03-22 | GSE227027 | GEO

SARS-CoV-2 Infection Induces Ferroptosis of Human Pluripotent Stem Cell-Derived Sinoatrial Nodal like Pacemaker Cells [single-cell RNA-seq]

Project description:We established an efficient strategy to derive functional human SAN like pacemaker cells for disease modeling and drug screening. We used a dual-reporter cell line(SHOX2-GFP+MYH6-mcherry) to indicate the sinoatrial nodal like pacemaker cells. We sorted out the double positive cell population after Day20 and prepared the sample for single cell RNA seq analysis.

2022-01-26 | GSE193723 | GEO

Epigenetic Profiling of Cardiac Pacemaker Cells Reveals a Conserved Isl1 Enhancer That Regulates Sinoatrial Node Development and Function

Project description:Cardiac pacemaker cells (PCs) in the sinoatrial node (SAN) have a distinct gene expression program that allows them to fire automatically and initiate the heartbeat. Although critical SAN transcription factors, including Isl1, have been identified, the cis-regulatory architecture that governs PC-specific gene expression is not understood, and discrete enhancers required for gene regulation in the SAN have not been identified. We used ATAC-Seq on sorted neonatal mouse SAN to define regions of open chromatin in PCs and neighboring right atrial cardiomyocytes. PC-specific ATAC-seq peaks were located near established SAN genes and were enriched for distinct sets of transcription factor binding sites. In-vivo testing of a novel ATAC-seq peak at the Isl1 locus defined a regulatory element that was active specifically in the cardiac inflow at E8.5 and throughout later SAN development and maturation. Deletion of the enhancer uncovered a role for this cis-regulatory element in SAN development and function. The mouse SAN enhancer also directed reporter activity to the inflow tract in developing zebrafish hearts, demonstrating deep conservation of its upstream regulatory network. Finally, single nucleotide polymorphisms in the human genome that occur near the region syntenic to the mouse enhancer exhibit significant associations with resting heart rate in human populations.

2020-10-12 | GSE148515 | GEO

Epigenetic Profiling of Cardiac Pacemaker Cells Reveals a Conserved Isl1 Enhancer That Regulates Sinoatrial Node Development and Function

Project description:Epigenetic Profiling of Cardiac Pacemaker Cells Reveals a Conserved Isl1 Enhancer That Regulates Sinoatrial Node Development and Function

| PRJNA624859 | ENA

Comparative iTRAQ analysis of proteomic expression in human sinoatrial node and working cardiomyocytes

Project description:The goal of this study was to assess the changes in protein expression in the human sinoatrial node (SAN) compared with working cardiomyocytes in order to identify specific SAN protein signatures. Four pair of samples (the SAN and working cardiomyocytes) were obtained post-mortem from four healthy human donors.

2018-03-05 | PXD004109 | Pride

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