Single cell sequencing of developing heart valves identifies novel cell populations and uncovers interstitial cell heterogeneity
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PROVIDER: PRJNA480856 | ENA |
REPOSITORIES: ENA
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Project description:This study has two main goals. The first is to define a gene expression atlas of heart valve cells and identify cell heterogeneity within postnatal heart valve development. The second is to identify interstitial cell populations involved in ECM remodeling during postnatal heart valve development. Overall design: Using droplet RNA sequencing, transcriptomes of single cells from P7 and P30 murine aortic and mitral heart valves were analyzed.
2018-07-13 | E-HCAD-18 | biostudies-arrayexpress
Project description:Our study has two main goals. The first is to define a gene expression atlas of heart valve cells and identify cell heterogeneity within postnatal heart valve development. The second is to identify interstitial cell populations involved in ECM remodeling during postnatal heart valve development.
2018-07-13 | GSE117011 | GEO
Project description:A disease driver population within interstitial cells of human calcific aortic valves identified via single-cell and proteomic profiling Cellular heterogeneity of aortic valves complicates mechanistic evaluation of the calcification processes in calcific aortic valve disease (CAVD), and animal disease models are lacking. In this study, we identify a disease driver population (DDP) within valvular interstitial cells (VICs). Through stepwise single-cell analysis, phenotype-guided -OMIC profiling, and network-based analysis, we characterize DDP fingerprint as CD44highCD29+CD59+CD73+CD45low and discover potential key regulators of human CAVD. These DDP-VICs demonstrate multi-lineage differentiation and osteogenic properties. Temporal proteomic profiling of DDP-VICs identifies potential targets for therapy, including MAOA and CTHRC1. In vitro loss-of-function experiments confirm our targets. Such a stepwise strategy may be advantageous for therapeutic target discovery in other disease contexts.
2022-01-24 | GSE194180 | GEO
Project description:Twist1, a basic helix-loop-helix transcription factor, is expressed in mesenchymal precursor populations during embryogenesis and in metastatic cancer cells. In the developing heart, Twist1 is highly expressed in endocardial cushion (ECC) valve mesenchymal cells and is down regulated during valve differentiation and remodeling. Previous studies demonstrated that Twist1 promotes cell proliferation, migration, and expression of primitive ECM molecules in ECC mesenchymal cells. Furthermore, Twist1 expression is induced in human pediatric and adult diseased heart valves. However, the Twist1 downstream target genes that mediate increased cell proliferation and migration during early heart valve development remain largely unknown. Candidate gene and global gene profiling approaches were used to identify direct transcriptional targets of Twist1 during heart valve development. Candidate target genes were analyzed for evolutionarily conserved regions (ECRs) containing E-box consensus sequences that are potential Twist1 binding sequences. ECRs containing conserved E-box sequences were identified for Twist1 responsive genes Tbx20, Cdh11, Sema3C, Rab39b, and Gadd45a. Twist1 binding to these sequences in vivo was determined by chromatin immunoprecipitation assays, and binding was detected in ECCs but not late stage remodeling valves. In addition identified Twist1 target genes are highly expressed in ECCs and have reduced expression during heart valve remodeling in vivo which is consistent with the expression pattern of Twist1. Together these analyses identify multiple new genes involved in cell proliferation and migration that are differentially expressed in the developing heart valves, are responsive to Twist1 transcriptional function, and contain Twist1 responsive regulatory sequences. Murine MC3T3-E1 preosteoblast cells were treated with siScrambled control or siTwist1 to achieve knockdown of Twist1. Both siScr and siTwist1 were performed in triplicate. Isolated RNA was analyzed with Affymetrix muring MOE 430 2.0 gene chip microarray.
2011-07-27 | E-GEOD-30953 | biostudies-arrayexpress
Project description:Twist1, a basic helix-loop-helix transcription factor, is expressed in mesenchymal precursor populations during embryogenesis and in metastatic cancer cells. In the developing heart, Twist1 is highly expressed in endocardial cushion (ECC) valve mesenchymal cells and is down regulated during valve differentiation and remodeling. Previous studies demonstrated that Twist1 promotes cell proliferation, migration, and expression of primitive ECM molecules in ECC mesenchymal cells. Furthermore, Twist1 expression is induced in human pediatric and adult diseased heart valves. However, the Twist1 downstream target genes that mediate increased cell proliferation and migration during early heart valve development remain largely unknown. Candidate gene and global gene profiling approaches were used to identify direct transcriptional targets of Twist1 during heart valve development. Candidate target genes were analyzed for evolutionarily conserved regions (ECRs) containing E-box consensus sequences that are potential Twist1 binding sequences. ECRs containing conserved E-box sequences were identified for Twist1 responsive genes Tbx20, Cdh11, Sema3C, Rab39b, and Gadd45a. Twist1 binding to these sequences in vivo was determined by chromatin immunoprecipitation assays, and binding was detected in ECCs but not late stage remodeling valves. In addition identified Twist1 target genes are highly expressed in ECCs and have reduced expression during heart valve remodeling in vivo which is consistent with the expression pattern of Twist1. Together these analyses identify multiple new genes involved in cell proliferation and migration that are differentially expressed in the developing heart valves, are responsive to Twist1 transcriptional function, and contain Twist1 responsive regulatory sequences.
2011-07-28 | GSE30953 | GEO
Project description:We performed single cell RNA sequencing (scRNA-seq) for 6,574 cells from the aortic valves of C57BL/6J (wild type), Ldlr-/-, and Apoe-/- mice. The extensive single cell profiles depicted hyperlipidemia-associated cellular dynamics in aortic valves.
2022-08-22 | GSE180278 | GEO
Project description:Aortic valves are collected from patients with severe aortic valve stenosis undergoing aortic valve replacement at the Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ), Quebec City, Canada. From this biobank collection, transcriptomic analyses from 240 aortic valves were performed. All valves were tricuspid and had a fibro-calcific remodeling score of 3 or 4. RNA was extracted from valve leaflets and gene expression evaluated using the Illumina HumanHT-12 v4 Expression BeadChip. The main objective of this study was to perform a large-scale expression quantitative trait loci (eQTL) mapping study on human aortic valves.
2018-03-14 | GSE102249 | GEO
Project description:Exploring the mechanisms of valvular heart disease (VHD) at the cellular level may be useful to identify new therapeutic targets; however, the comprehensive cellular landscape of non-diseased human cardiac valve leaflets remains unclear. The cellular landscapes of non-diseased human cardiac valve leaflets (five aortic valves, five pulmonary valves, five tricuspid valves, and three mitral valves) from end-stage heart failure patients undergoing heart transplantation were explored using single-cell RNA sequencing (scRNA-seq)
2022-09-13 | GSE213128 | GEO
Project description:Semilunar valve leaflets have a well-described trilaminar histoarchitecture with a sophisticated elastic fiber network. It was previously proposed that elastin-containing fibers play a subordinate role in early human cardiac valve development; however, this assumption was based on data obtained from mouse models and human second and third trimester tissues. Here, we systematically analyzed tissues from human fetal first (4-12 weeks) and second (13-18 weeks) trimester, adolescent (14-19 years) and adult (50-55 years) hearts to monitor the temporal and spatial distribution of elastic fibers, focusing on semilunar valves. Global gene expression analyses revealed that the transcription of genes essential for elastic fiber formation starts early within the first trimester. These data were confirmed by quantitative PCR and immunohistochemistry employing antibodies that recognize fibronectin, fibrilin-1, -2 and -3, EMILIN-1, fibulin-4 and fibulin-5, which were all expressed at the onset of cardiac cushion formation (~week 4 of development). Tropoelastin/ elastin protein expression was first detectable in leaflets of 7-week hearts. We revealed that immature elastic fibers are organized in early human cardiovascular development, and mature elastin-containing fibers first evolve in semilunar valves when blood pressure and heartbeat accelerate. Our findings provide a conceptual framework with the potential to lead to novel hypotheses in human cardiac valve development and disease. Total RNA obtained from fetal cardiac valve cushions, developed fetal heart valves, adolescent heart valves, and adult heart valves.
2013-04-06 | E-GEOD-45821 | biostudies-arrayexpress
Project description:Several microRNAs (miRNAs) have been identified to play crucial roles in calcificated aortic valves disease, numerous miRNAs are still waiting to be explored. In this study, we compared the miRNA expression profiles of human non-calcified (n=3) and calcified (n=5) aortic valves, and found that compared with the normal control valves, 152 miRNAs were up-regulated and 186 miRNAs were down-regulated in calcified aortic valves. Among the top hit down-regulated miRNAs, we found that the expression level of miR-139-5p was negatively correlated with the osteogenic genes RUNX2 and BMP3, and was also down-regulated during the osteogenic differentiation of primary human aortic VICs.
2021-12-31 | GSE171208 | GEO