The effects of primary cilia on endothelial gene expression exposed to flow
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ABSTRACT:
PROVIDER: PRJNA580367 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10363100.fastq.gz | Fastqsanger.gz | |||
| SRR10363101.fastq.gz | Fastqsanger.gz | |||
| SRR10363102.fastq.gz | Fastqsanger.gz | |||
| SRR10363103.fastq.gz | Fastqsanger.gz | |||
| SRR10363104.fastq.gz | Fastqsanger.gz |
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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
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
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
Project description:The luminal surface of the endothelium is exposed to dynamic blood flow patterns that are known to affect endothelial cell phenotype. In this study, human aortic endothelial cells (HAECs) were exposed to unidirectional laminar flow (20 dynes/cm2) or disturbed flow (±4 dynes/cm2, 2 Hz) for 48 hrs and then subjected to RNA sequencing. The sequencing data was used to analyze changes in endothelial cell gene expression and pathways associated with lipid metabolism.
2024-07-01 | GSE266437 | GEO
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
Project description:Under pressure: altered endothelial flow response.
| PRJNA1085195 | ENA
Project description:Biomechanical forces influence vascular function, but the molecular mechanisms regulating many of these mechano-activated cellular events remain largely uncharacterized. In particular, the vascular endothelium can sense alterations in hemodynamic shear stress which, in the context of adaptive remodeling or arteriogenesis, has been shown to lead to the generation of endothelial-derived signals critical for controlling blood vessel structure and function. Here, we sought to define the arteriogenic responses evoked in endothelial cells exposed to flow using transciptional profiling. Analysis of these transcriptional programs identified several genes previously shown to be important for endothelial-smooth muscle interactions and vascular remodeling, including the transcription factor kruppel-like factor 2 (KLF2).
2009-01-01 | GSE11583 | GEO
Project description:Blood flow within the vasculature is a critical determinant of endothelial cell (EC) identity and functionality, yet the intricate interplay of various hemodynamic forces and their collective impact on endothelial and vascular responses are not fully understood. Specifically, the role of hydrostatic pressure in the context of flow response is understudied, despite its known significance in vascular development and disease. To address this gap, we developed in vitro models to investigate how pressure influences EC responses to flow. Our study demonstrates that elevated pressure conditions significantly modify shear-induced flow alignment and increase endothelial cell density, a phenomenon often observed in vascular diseases. Utilizing both bulk and single-cell RNA sequencing, we found that while flow is the primary driver of transcriptional changes from static conditions, pressure distinctly modulates this flow response by upregulating gene sets linked to arterial cell phenotypes. Conserved pressure-responsive transcriptional signatures identified in human ECs were upregulated during the onset of circulation in early mouse embryonic vascular development, where pressure was notably associated with transcriptional programs essential to arterial and hemogenic EC fates. Our findings emphasize the necessity of an integrative approach to endothelial cell mechanotransduction, one that encompasses the effects induced by pressure alongside other hemodynamic forces.
2024-03-12 | GSE261063 | GEO
Project description:Objective The vessel wall is continuously exposed to hemodynamic forces generated by blood flow. Endothelial mechanosensors perceive and translate mechanical signals via cellular signaling pathways into biological processes that control endothelial development, phenotype and function. Here, we aim to unravel the molecular mechanisms underlying endothelial mechanosensing. Approach and results We applied a quantitative mass spectrometry approach combined with cell surface chemical footprinting to assess the hemodynamic effects on the endothelium on a system-wide level. These studies revealed that of the >5000 quantified proteins 104 were altered, which were highly enriched for extracellular matrix proteins and proteins involved in cell-matrix adhesion. Cell surface proteomics furthermore indicated that LAMA4 was proteolytically processed upon flow-exposure, which corresponded to the decreased LAMA4 mass observed on immunoblot. Immunofluorescence microscopy studies highlighted that the endothelial basement membrane was drastically remodeled upon flow exposure. We observed a network-like pattern of LAMA4 and LAMA5, which corresponded to the localization of laminin-adhesion molecules ITGA6 and ITGB4. Furthermore, the adaptation to flow-exposure did not affect the inflammatory response to tumor necrosis factor α, indicating that inflammation and flow trigger fundamentally distinct endothelial signaling pathways with limited reciprocity and synergy. Conclusions Taken together, this study uncovers the blood flow-induced remodeling of the basement membrane and stresses the importance of the subendothelial basement membrane in vascular homeostasis.
2020-04-29 | PXD014526 | Pride
Project description:The arterial endothelium’s response to its flow environment is critical to vascular homeostasis. The endothelial glycocalyx has been shown to play a major role in mechanotransduction, but the extent to which the components of the glycocalyx affect the overall function of the endothelium remains unclear. The objective of this study was to further elucidate the role of heparan sulfate as a mechanosensor on the surface of the arterial endothelium, by (1) expanding the variety of shear waveforms investigated, (2) continuously suppressing heparan sulfate expression rather than using a pre-flow batch treatment, and (3) performing microarray analysis on post-flow samples. Porcine aortic endothelial cells were exposed to non-reversing, reversing, and oscillatory shear waveforms for 24 hours with or without continuous heparan sulfate suppression with heparinase. All shear waveforms significantly increased the amount of heparan sulfate on the surface of the endothelium. Suppression of heparan sulfate to less than 25% of control levels did not inhibit shear-induced cell alignment or nitric oxide production, or alter gene expression, for any of the shear waveforms investigated. We infer that heparan sulfate on the surface of porcine aortic endothelial cells is not the primary mechanosensor for many shear-responsive endothelial cell functions in this species. Porcine aortic endothelial cells were exposed to 3 different shear waveforms for 24 hours with or without the addition of 300 mU/ml heparinase III to the flow media. The shear waveforms inculded Non-reversing (15 ± 15 dyne/cm2, 1 Hz), Steady (15 dyne/cm2), or Oscillatory (0 ± 15 dyne/cm2, 1 Hz) shear. Four replicates of each condition were performed for a total of 24 experiments. Each experimental sample was hybridized to an oligonucleotide array along with a standard reference sample (static cells).
2011-07-21 | E-GEOD-30843 | biostudies-arrayexpress