Joint single-cell/single-nucleus RNA-seq on hearts from healthy or HFpEF mice
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ABSTRACT:
PROVIDER: PRJEB66293 | ENA |
REPOSITORIES: ENA
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Project description:In this project we explore the cellular heterogeneity of a mouse model of heart failure with preserved ejection fraction (HFpEF) involving a two-hit model of feeding a high fat diet (HFD) along with L-NAME administration. Healthy adult male mice (C57BL/6J inbred) were fed either a normal chow diet or HFD/L-NAME for 10 weeks or 15 weeks before performing sequencing experiments. Both cardiomyocytes (CMs) and total interstitial population (TIP) were captured using a protocol to jointly capture and sequence single-nuclei (for cardiomyocytes) and single-cells (for TIP) using the 10x Genomics Chromium system.
2024-05-08 | E-MTAB-13362 | biostudies-arrayexpress
Project description:This study was undertaken to assess transcriptional and epigenetic heterogeneity a the level of individual cells within neuroblastoma cell lines, and to compare cell lines with MYCN amplificaion to cell lines without MYCN amplification. Methods: We used 10X Genomics multiome sequencing technology to perform joint gene expression and ATAC profiling on thousands of nuclei isolated from the following human neuoblastoma cell lines: SHSY5Y, SK-N-AS, SK-N-SH, SK-N-DZ, Be-2c, and CHP134. Results: We found considerable gene expression and epigeneic heterogeneity both within and between neuroblastoma cell lines. Conclusion: Joint single-nucleus RNA sequencing and single-nucleus ATAC sequencing has demonsrated that neuroblastoma cell lines are heterogeneous, which may have implications for therapeutic strategies.
2024-09-17 | GSE262189 | GEO
Project description:Joint single-nucleus RNA sequencing and single-nucleus ATAC sequencing of neuroblastoma cell lines
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Project description:MultiPerturb-seq is a high-throughput CRISPR screening platform with joint single nucleus chromatin accessibility, transcriptome, and guide RNA capture. It uses combinatorial indexing combined with droplet microfluidics to scale throughput and integrate all three modalities. We apply MultiPerturb-seq to identify key genes whose loss can trigger differentiation in a rare pediatric cancer, atypical teratoid/rhabdoid tumor (AT/RT), which is driven by loss of the SWI/SNF chromatin remodeling subunit SMARCB1.
2024-09-22 | GSE277747 | GEO
Project description:MultiPerturb-seq is a high-throughput CRISPR screening platform with joint single nucleus chromatin accessibility, transcriptome, and guide RNA capture. It uses combinatorial indexing combined with droplet microfluidics to scale throughput and integrate all three modalities. We apply MultiPerturb-seq to identify key genes whose loss can trigger differentiation in a rare pediatric cancer, atypical teratoid/rhabdoid tumor (AT/RT), which is driven by loss of the SWI/SNF chromatin remodeling subunit SMARCB1.
2024-10-13 | GSE278910 | GEO
Project description:Single nucleus RNA-seq of cardiomyocytes from neonatal mouse hearts after injury
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Project description:We have demonstrated previously that adult cardiomyocytes can dedifferentiate and proliferate when cultured in vitro. To determine if cardiomyocyte dedifferentiation and cell cycling/proliferation happens in vivo, we applied here a novel multi-reporter transgenic mouse model (aMH-CMerCreMer;mT/MG;aMHC-H2BBFP) carrying reporter genes for permanent cardiomyocyte lineage mapping and maturity (dedifferentiation) reporting. With this new model, we deciphered the cellular sources and processes of cardiomyocyte dedifferentiation and proliferation in adult hearts. In this study, we used single-nucleus RNA-sequencing to tackle the challenges in analyzing the highly heterogeneous heart cell populations, and obtained datasets for a large number of cardiac single nuclei (both myocytes and non-myocytes) for control and post-infarct hearts. We identified specific cell populations in the heart using distinct transcriptomic clusters, transgenic reporters for ACM lineage and dedifferentiation, as well as cell cycle markers. The results demonstrated that the dedifferentiation and cell cycle progression of pre-existing CMs was augmented in post-infarct hearts, with a number of signaling pathways and gene sets affected. This is the first study dissecting the transcriptomic profiles and signaling pathways associated with cardiomyocyte dedifferentiation and cycling/proliferation in vivo using unbiased high-throughput single-nucleus RNA-Seq analysis, in junction with novel cell lineage (e.g. cardiomyocyte) and phenotyping (e.g. dedifferentiation) transgenic model systems.
2019-07-02 | GSE128628 | GEO
Project description:A fundamental challenge in understanding cardiac biology and disease is that the remarkable heterogeneity in cell-type composition and functional states have not been well characterized at single-cell resolution in maturing and diseased mammalian hearts. Massively parallel single-nucleus RNA sequencing (snRNA-Seq) has emerged as a powerful tool to address these questions by interrogating the transcriptome of tens of thousands of nuclei isolated from fresh or frozen tissues. snRNA-Seq overcomes the technical challenge of isolating intact single cell from complex tissues including the maturing mammalian hearts, reduces biased recovery of easily dissociated cell types and minimizes aberrant gene expression during the whole-cell dissociation. Here we applied sNucDrop-Seq, a droplet microfluidics-based massively parallel snRNA-Seq method, to investigate the transcriptional landscape of postnatal maturing mouse hearts in both healthy or disease state. By profiling the transcriptome of nearly 20,000 nuclei, we identified major and rare cardiac cell types and revealed significant heterogeneity of cardiomyocytes, fibroblasts and endothelial cells in the postnatal developing heart. When applied to a mouse model of pediatric mitochondrial cardiomyopathy, we uncovered profound cell type-specific modifications of the cardiac transcriptional landscape at single-nucleus resolution, including changes of subtype composition, maturation states and functional remodeling of each cell type. Furthermore, we employed sNucDrop-Seq to decipher the cardiac cell type-specific gene regulatory network (GRN) of GDF15, a heart-derived hormone and clinically important diagnostic biomarker of heart disease. Together, our results present a rich resource for studying cardiac biology and provide new insights into heart disease using an approach broadly applicable to many fields of biomedicine.
2018-10-01 | GSE118545 | GEO
Project description:Aims: Despite the high prevalence of heart failure with preserved ejection fraction (HFpEF), the pathomechanisms remain elusive and specific therapy is lacking. Disease-causing factors include metabolic risk, notably obesity. However, proteomic changes in HFpEF are poorly understood, hampering therapeutic strategies. We sought to elucidate how metabolic syndrome affects cardiac protein expression, phosphorylation and acetylation in the Zucker diabetic fatty/Spontaneously hypertensive heart failure F1 (ZSF1) rat HFpEF model, and to evaluate some changes regarding their potential for treatment. Main methods: ZSF1 obese and lean rats were fed a Purina diet up to the onset of HFpEF in the obese animals. We quantified the proteome, phosphoproteome and acetylome of ZSF1 obese versus lean heart tissues by mass spectrometry and singled out targets for site-specific evaluation. Key findings: We found the acetylome of ZSF1 obese versus lean hearts more severely altered (21% of proteins changed) than the phosphoproteome (9%) or proteome (3%). Proteomic alterations, confirmed by immunoblotting, indicated low-grade systemic inflammation and endothelial remodeling in obese hearts, but low nitric oxide-dependent oxidative/nitrosative stress. Altered acetylation in ZSF1 obese hearts mainly affected pathways important for metabolism, energy production and mechanical function, including hypo-acetylation of mechanical proteins but hyper-acetylation of proteins regulating fatty acid metabolism. Hypo-acetylation and hypo-phosphorylation of elastic titin in ZSF1 obese hearts explained myocardial stiffening. Significance: Cardiometabolic syndrome alters posttranslational modifications, notably acetylation, in experimental HFpEF. Pathway changes implicate a HFpEF signature of low-grade inflammation, endothelial dysfunction, metabolic and mechanical impairment, and suggest titin stiffness and mitochondrial metabolism as promising therapeutic targets.
2022-10-12 | PXD036259 | Pride
Project description:The adult mammalian heart is incapable of regeneration following injury. In contrast, the neonatal mouse heart can efficiently regenerate during the first week of life. The molecular mechanisms that mediate the regenerative response and its blockade in later life are not understood. Here, by single-nucleus RNA sequencing, we map the dynamic transcriptional landscape of five distinct cardiomyocyte populations in healthy, injured and regenerating mouse hearts. We identify immature cardiomyocytes that enter the cell-cycle following injury and disappear as the heart loses the ability to regenerate. These proliferative neonatal cardiomyocytes display a unique transcriptional program dependent on NFYa and NFE2L1 transcription factors, which exert proliferative and protective functions, respectively. Cardiac overexpression of these two factors conferred protection against ischemic injury in mature mouse hearts that were otherwise non-regenerative. These findings advance our understanding of the cellular basis of neonatal heart regeneration and reveal a transcriptional landscape for heart repair following injury.
2020-03-18 | GSE130699 | GEO