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Endocardial primary cilia and blood flow regulate EndoMT during endocardial cushion development [Single Nuc-RNAseq_IFT]

ABSTRACT: Endocardial primary cilia and blood flow regulate EndoMT during endocardial cushion development [Single Nuc-RNAseq_IFT]

PROVIDER: PRJNA1060257 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27400285.fastq.gz	Fastqsanger.gz
	SRR27400286.fastq.gz	Fastqsanger.gz
	SRR27400287.fastq.gz	Fastqsanger.gz
	SRR27400288.fastq.gz	Fastqsanger.gz
	SRR27400289.fastq.gz	Fastqsanger.gz

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Similar Datasets

Endocardial primary cilia and blood flow regulate EndoMT during endocardial cushion development [Single Nuc-RNAseq_IFT]

Project description:Blood flow is critical for heart valve formation, and cellular mechanosensors are essential to translate flow into transcriptional regulation of development. Here, we identify a role for primary cilia in vivo in the spatial regulation of cushion formation, the first stage of valve development, by regionally controlling endothelial to mesenchymal transition (EndoMT) via modulation of Kruppel-like Factor 4 (Klf4). We find that high shear stress intracardiac regions decrease endocardial ciliation over cushion development, correlating with KLF4 downregulation and EndoMT progression. Mouse embryos constitutively lacking cilia exhibit a blood-flow dependent accumulation of KLF4 in these regions, independent of upstream left-right abnormalities, resulting in impaired cushion cellularization. snRNA-seq revealed that cilia KO endocardium fails to progress to late-EndoMT, retains endothelial markers and has reduced EndoMT/mesenchymal genes that KLF4 antagonizes. Together, these data identify a mechanosensory role for endocardial primary cilia in cushion development through regional regulation of KLF4.

2025-06-16 | GSE252341 | GEO

Endocardial primary cilia and blood flow regulate EndoMT during endocardial cushion development [Single Nuc-RNAseq_NCX]

Project description:Blood flow is critical for heart valve formation, and cellular mechanosensors are essential to translate flow into transcriptional regulation of development. Here, we identify a role for primary cilia in vivo in the spatial regulation of cushion formation, the first stage of valve development, by regionally controlling endothelial to mesenchymal transition (EndoMT) via modulation of Kruppel-like Factor 4 (Klf4). We find that high shear stress intracardiac regions decrease endocardial ciliation over cushion development, correlating with KLF4 downregulation and EndoMT progression. Mouse embryos constitutively lacking heart contractility do not upregulate KLF4 or undergo EndoMT. snRNA-seq revealed that Ncx1-/- embryos failed to transition to early-EndoMT and have reduced mesenchymal markers.

2025-06-16 | GSE293814 | GEO

Endocardial primary cilia and blood flow regulate EndoMT during endocardial cushion development [Single Nuc-RNAseq_NCX]

Project description:Endocardial primary cilia and blood flow regulate EndoMT during endocardial cushion development [Single Nuc-RNAseq_NCX]

| PRJNA1246502 | ENA

The effects of primary cilia on endothelial gene expression exposed to flow

Project description:Biomechanical forces such as wall shear stress induced by flowing blood influence the behavior of vascular cells and have been shown to be crucial in the onset of vascular disease. Primary cilia are increasingly recognized as important biological sensors of low WSS. The goal of the study was to investigate gene expression profile of endothelial cell under low flow (2 dynes/cm2) as compared to physiological flow (30 dynes/cm2) in presence or absence of primary cilia.

2022-05-25 | GSE139580 | GEO

Spatial Transcriptional Profile of the Chick and Mouse Endocardial Cushions Identify Novel Regulators of Endocardial EMT in vitro

Project description:Objective: We developed an unbiased strategy to identify genes important in endocardial epithelial-to-mesenchymal transformation (EMT) using a spatial transcriptional profile. Methods and Results: Endocardial cells overlaying the cushions of the atrioventricular canal (AVC) and outflow tract (OFT) undergo an EMT to yield VICs. RNA sequencing (RNA-seq) analysis of gene expression between AVC, OFT, and ventricles (VEN) isolated from chick and mouse embryos at comparable stages of development (chick HH18; mouse E11.0) was performed. EMT occurs in the AVC and OFT cushions, but not VEN at this time. 210 genes in the chick (n=1) and 105 genes in the mouse (n=2) were enriched 2-fold in the cushions. Gene regulatory networks (GRN) generated from cushion-enriched gene lists confirmed TGFβ as a nodal point and identified NF-κB as a potential node. To reveal previously unrecognized regulators of EMT four candidate genes, Hapln1, Id1, Foxp2, and Meis2, and a candidate pathway, NF-κB, were selected. In vivo spatial expression of each gene was confirmed by in situ hybridization and a functional role for each in endocardial EMT was determined by siRNA knockdown in a collagen gel assay. Conclusions: Our spatial-transcriptional profiling strategy yielded gene lists which reflected the known biology of the system. Further analysis accurately identified and validated previously unrecognized novel candidate genes and the NF-κB pathway as regulators of endocardial cell EMT in vitro. 3 separate regions of the developing heart tube were dissected and processed for RNA sequencing analysis in both HH18 chick and E11.0 ICR mouse (done in duplicate)

2013-04-16 | E-GEOD-43194 | biostudies-arrayexpress

Spatial Transcriptional Profile of the Chick and Mouse Endocardial Cushions Identify Novel Regulators of Endocardial EMT in vitro

2013-04-16 | GSE43194 | GEO

Primary cilia sensing-regulated transcriptome in the collecting duct

Project description:RNA-seq technology was used to reveal the transcriptome changes of tubular epithelia in response to fluid flow and determine the role of primary cilia in this process. Many fluid flow-sensitive genes were identified, among which are those regulated by primary cilia sensing of fluid flow. These genes were further validated by RT-qPCR.

2018-01-27 | GSE109701 | GEO

The effects of primary cilia on endothelial gene expression exposed to flow

Project description:The effects of primary cilia on endothelial gene expression exposed to flow

| PRJNA580367 | ENA

Genome-wide Twist1 occupancy in endocardial cushion cells, embryonic limb buds, and peripheral nerve sheath tumor cells

Project description:The basic helix-loop-helix transcription factor Twist1 has a well-documented role in mesenchymal populations of the developing embryo, such as endocardial cushion (ECC) mesenchymal cells and limb buds, and during cancer development and progression. Whether Twist1 regulates the same transcriptional targets in different cell types has yet to be investigated. Through chromatin immunoprecipitation followed by sequencing (Chip-seq) analysis, the cell type-specific genome-wide occupancy of Twist1 was investigated in ECCs, limb buds and mouse peripheral nerve sheath tumor (PNST) cells. Twist1 binds mainly in a cell type-specific manner, with very few common genomic regions occupied by Twist1 in different cell types. Genes associated with binding peaks in each cell type are related to known Twist1 cellular functions in ECCs, limb buds, and cancer cells. We found that cell type-specific binding of Twist1 may be influenced by histone modifications or co-factors. Binding regions were located in several Wnt pathway associated genes, supporting a link between Twist1 and Wnt signalling in ECCs, limb buds, and PNST cells. These data suggest that similar functions are regulated by Twist1 in ECCs, limb buds, and PNST cells in a cell type-specific manner, and provide insights into possible mechanisms utilized for cell type-specificity of Twist1 binding. We compare Twist1 genome occupancy in mouse embryonic day (E) 12.5 endocardial cushion mesenchymal cells, E10.5 forelimb buds, and a mouse peripheral nerve sheath tumor cell line.

2014-10-02 | E-GEOD-50111 | biostudies-arrayexpress

Regional differences in left ventricular shear stress contribute to heterogenity of the endocardial transcriptome

Project description:The role of shear stress, the frictional force of blood flow, on the endothelium has been well documented. Differences in shear stress can have profound effects on endothelial and blood vessel biology. Endothelial cells (ECs), termed endocardial ECs, line the heart chambers and are exposed to complex shear stress patterns. While it has been demonstrated that shear stress is important for heart development, little has been shown on the role of shear stress on adult ECs. 4D-MRI studies demonstrate regional differences in blood residence time. We sought to determine the effect of regional differences in endocardial shear stress on the endocardial transcriptome using RNA sequencing (RNA-seq) on 3 different regions (apex, mid-ventricle, outflow tract) from 8 adult pigs, for a total of 24 RNA-seq assays.

2015-12-31 | E-MTAB-3669 | biostudies-arrayexpress

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