Age-Dependent Transcriptional Alterations in Cardiac Endothelial Cells [bulk RNA-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA687688 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13302400.fastq.gz | Fastqsanger.gz | |||
| SRR13302401.fastq.gz | Fastqsanger.gz | |||
| SRR13302402.fastq.gz | Fastqsanger.gz | |||
| SRR13302403.fastq.gz | Fastqsanger.gz | |||
| SRR13302404.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 20 |
Similar Datasets
Project description:Purpose: The goal of this study is to determine alterations in heart endothelial cell transcripts associated with aging. This is accomplished by comparing endothelial transcriptomes from young and aged organs (heart, brain and kidney). Methods: Endothelial mRNA profiles of 3 month and 24 month old wild-type mice were generated by next generation sequencing using libraries generated via SmartSeq V4 chemistry (Takara) and sequenced on an HiSeq 2500 (Illuina). Tophat2 with default parameters was used to align the sequenced reads against the mouse genome using the GRCm38. HTSeq python software with default parameters was used to quantify the transcripts of the aligned reads using the corresponding GRCm38 gene annotation model from Ensembl. Results: Highly enriched populations of endothelial cells (ECs) isolated from the heart, brain and kidney of young (3 months) and old (24 months) C57/BL6 mice were profiled for RNA expression via bulk RNA sequencing. Approximately 700 cardiac endothelial transcripts significantly differ by age. Gene set enrichment analysis indicated similar patterns for cellular pathway perturbations. Receptor-ligand comparisons indicated parallel alterations in age-affected circulating factors and cardiac endothelial-expressed receptors. Single-cell RNA-seq analysis identified 9 distinct endothelial cell subtypes in the heart with an age-associated population shift observed for an Aplnr-enriched endothelial cell clusters. Conclusions: Gene and pathway enrichment analyses show that age-related transcriptional response of cardiac endothelial cells is distinct from that of endothelial cells derived from the brain or kidney vascular bed. Furthermore, single-cell analysis identified 9 distinct EC subtypes, and shows that Aplnr-enriched subtype is reduced with age in mouse heart. Finally, we identify age-dysregulated genes in specific aged cardiac endothelial subtypes.
2021-05-28 | GSE163821 | GEO
Project description:Age-Dependent Transcriptional Alterations in Cardiac Endothelial Cells
| PRJNA687680 | ENA
Project description:Age-Dependent Transcriptional Alterations in Cardiac Endothelial Cells [scRNA-seq]
| PRJNA687689 | ENA
Project description:Purpose: The goal of this study is to determine alterations in heart endothelial cell transcripts and cell populations associated with aging. Methods: Endothelial single cell mRNA profiles of 3 month and 24 month old wild-type mice were generated by 10X Genomics Results: Using an optimized data analysis workflow, we mapped about 50 thousand reads per cell Conclusions: Our study represents the first analysis of aged cardiac endothelial cell transcriptomes using single cell RNA-seq technology, identifiying specific transcripts and cell populations affected by age.
2021-05-28 | GSE163822 | GEO
Project description:In mouse aorta endothelial cells, populations of endothelial vascular progenitor (EVP) and differentiated (D) cells could be identified by CD31 (lo/hi) and VEGFR2 (lo/hi) expression. These populations were FACS sorted and paired-end bulk RNA-sequencing was performed.
2019-05-27 | E-MTAB-7148 | biostudies-arrayexpress
Project description:C57BL6/J mice were treated with anti-PD-1 for 2 or 4 weeks, or with isotype control antibody. In echocardiography, cardiac dysfunction was seen both after 2 and 4 weeks, with decreased ejection fraction and left ventricular dilation. Bulk RNA sequencing of the hearts after treatment was performed to identify the mechanisms of anti-PD-1-induced cardiac dysfunction.
2022-12-03 | E-MTAB-12388 | biostudies-arrayexpress
Project description:The meningeal lymphatic network—housed within the dural meninges surrounding the brain— is critical for cerebrospinal fluid (CSF) drainage. Through continuous brain interstitial fluid (ISF) mixing with CSF via the glymphatic system, this lymphatic network facilitates the removal of central nervous system (CNS) waste. During aging and in Alzheimer’s disease (AD), attenuated meningeal lymphatic drainage promotes the buildup of toxic misfolded proteins—including amyloid beta—in the CNS. Alleviating this age-related meningeal lymphatic dysfunction represents a promising therapeutic strategy to alleviate AD pathology. However, the mechanisms underlying this lymphatic decline remain elusive. Here we demonstrate that age-related alterations in meningeal immunity contribute to meningeal lymphatic impairment. Single-cell RNA-sequencing of dural lymphatic endothelial cells in aged mice demonstrated a response signature to the cytokine IFNγ, which was elevated in the aged dura due to meningeal T cell accumulation. Chronic elevation of IFNγ in the meninges of young mice via AAV-mediated overexpression altered lymphatic adherans junctions and impaired CSF drainage to deep cervical lymph nodes—comparable to the deficits observed in aged mice. Direct disruption of lymphatic junctions via CSF-delivered VE-Cadherin disrupting antibodies was sufficient to phenocopy impairments in CSF drainage. Therapeutically, IFNγ neutralization in aged mice alleviated age-related impairments in meningeal lymphatic function. These data suggest manipulation of meningeal immunity as a viable therapeutic target to normalize CSF drainage in aged mice and alleviate the pathology in AD mice associated with impaired waste removal.
2023-03-10 | GSE217276 | GEO
Project description:Insulin-like growth factor (IGF1R) signalling has been implicated to play an important role in regulation of cardiac growth, hypertrophy and contractile function, and has been linked to the development of age related congestive heart failure. Here we address the question to what extent cardiomyocyte specific IGF1 signalling is essential for maintenance of the structural and functional integrity of the adult murine heart. To investigate the effects of IGF1 signalling in the adult heart without confounding effects due to IGF1 over-expression or adaptation during embryonic and early post-natal development, we inactivated the IGF1R by a 4-hydroxy tamoxifen inducible Cre recombinase in adult cardiac myocytes. Efficient inactivation of the IGF1R (iCMIGF1RKO) as assessed by Western analysis and real-time PCR went along with reduced IGF1-dependent AKT and GSK3β-phosphorylation. Functional analysis by conductance manometry and magnetic resonance imaging (MRI) revealed no functional alterations in young adult iCMIGF1RKO mice (age 3 month). However, when induced in aged mice (11 month) diastolic cardiac function was depressed. To address the question if insulin signalling might compensate for the defective IGF1R signalling we inactivated β-cells by streptozotocin. However, the diabetes associated functional depression was similar in controls and iCMIGF1RKO mice. Similarly, analysis of the cardiac gene expression profile on 44K microarrays did not reveal activation of overt adaptive processes. Endogenous IGF1 receptor signalling is required for conservation of cardiac function of the aging heart, but not for the integrity of cardiac structure and function of young hearts. Four samples of each group: the control group, positive for Cre recombinase, but negative for the floxed IGF-1R and the experimental group with double transgenic mice (merCremer/+ IGFloxP/IGFloxP).
2012-07-31 | E-GEOD-32936 | biostudies-arrayexpress
Project description:Adult endothelial cells (ECs) are known to possess organ-specific gene expression, morphology and function, but whether organ-specific EC gene expression is present during human development is not known. Here, we used bulk RNA-sequencing (RNA-seq) to interrogate the developing human intestine, lung, and kidney in order to identify organ-enriched EC-gene signatures. FACS was used to isolate EC (CD31+CD144+, n=13) and non-EC (CD31-CD144-, n=16) populations from these three organs, profiling at least 4 biological replicates for each organ system. The biological specimens profiled were between 11-20 gestational weeks. We also sequenced cultured human umbilical vein endothelial cells (HUVECs) via bulk RNAseq. Computational approaches were used to identify organ-specific EC-enriched gene signatures across human fetal lung, intestine, and kidney ECs.
2020-12-20 | E-MTAB-9372 | biostudies-arrayexpress
Project description:As we age, structural changes contribute to progressive decline in organ function, which in the heart acts through poorly characterized mechanisms. Utilizing the rapidly aging fruit fly model with its significant homology to the human cardiac proteome, we found that cardiomyocytes exhibit progressive loss of Lamin C (mammalian Lamin A/C homologue) with age. Unlike other tissues and laminopathies, we observe decreasing nuclear size, while nuclear stiffness increases. Premature genetic reduction of Lamin C phenocopies aging’s effects on the nucleus, and subsequently decreases heart contractility and sarcomere organization. Surprisingly, Lamin C reduction downregulates myogenic transcription factors and cytoskeletal regulators, possibly via reduced chromatin accessibility. Subsequently, we find an adult-specific role for cardiac transcription factors and show that maintenance of Lamin C sustains their expression and prevents age-dependent cardiac decline. Our findings are conserved in aged non-human primates and mice, demonstrating age-dependent nuclear remodeling is a major mechanism contributing to cardiac dysfunction.
2022-11-01 | GSE185967 | GEO