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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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			Action	DRS
	SRR11194840.fastq.gz	Fastqsanger.gz
	SRR11194841.fastq.gz	Fastqsanger.gz
	SRR11194842.fastq.gz	Fastqsanger.gz
	SRR11194843.fastq.gz	Fastqsanger.gz
	SRR11194844.fastq.gz	Fastqsanger.gz

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Single-cell transcriptome analysis reveals CD34 as a marker of human sinoatrial node pacemaker cardiomyocytes [hPSC_SAN]

Project description:The sinoatrial node regulates the heart rate throughout life. Failure of this primary pacemaker results in life-threatening, slow heart rhythm. Despite its important function, the cellular and molecular composition of the human sinoatrial node is not resolved. Particularly, no cell surface marker to identify and isolate sinoatrial node pacemaker cells has been reported. Here we use single-nuclei/cell RNA sequencing of fetal and human pluripotent stem cell-derived sinoatrial node cells and show that they consist of three subtypes of pacemaker cells, including Core Pacemaker, Sinus Venosus, and Transitional Cells. Our study identifies a host of sinoatrial node pacemaker markers including MYH11, BMP4, and the cell surface antigen CD34. We demonstrate that sorting for CD34+ cells from stem cell differentiation cultures enriches for sinoatrial node cells with a functional pacemaker phenotype. This sinoatrial node pacemaker cell surface marker is highly valuable for stem cell-based disease modelling, drug discovery, cell replacement therapies, as well as the delivery of therapeutics to sinoatrial node cells in vivo using antibody-drug conjugates.

2024-10-30 | GSE279631 | GEO

Single-cell transcriptome analysis reveals CD34 as a marker of human sinoatrial node pacemaker cardiomyocytes [fetal SAN]

2024-10-30 | GSE279630 | GEO

Single-cell transcriptome analysis reveals CD34 as a marker of human sinoatrial node pacemaker cardiomyocytes [CITE-seq]

2024-10-30 | GSE279632 | GEO

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

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

Mouse sinoatrial node transcriptome

2015-02-06 | GSE65658 | GEO

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

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