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RNAseq of mitral valves from Fbn1 C1039G/+ mice with or without CCR2 deficiency

ABSTRACT: RNAseq of mitral valves from Fbn1 C1039G/+ mice with or without CCR2 deficiency

PROVIDER: PRJNA837252 | ENA |

REPOSITORIES: ENA

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RNAseq of mitral valves from Fbn1 C1039G/+ mice with or without CCR2 deficiency

Project description:Mitral valves were isolated from 2-month-old mice with the following 4 genotypes: 1) CCR2 RFP/+ (Chet), 2) CCR2 RFP/RFP (Cko), 3) Fbn1 C1039G/+; CCR2 RFP/+ (FhetChet), 4) Fbn1 C1039G/+; CCR2 RFP/RFP (FhetCko). N=4 for each genotype. Total RNA was extracted from mitral valves individually for gene expression profiling.

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RNAseq of mitral valves from Fbn1 mutant and control mice at 5 months

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RNAseq of mitral valves from Fbn1 mutant and control mice at 5 months

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Gene expression profile at single cell level from mitral valves of wild-type and Fbn1 C1039G/+ mice at 1 month-of-age

Project description:Myxomatous valve disease is the most common form of heart valve disease leading to morbidity and mortality worldwide. It is primarily associated with inherited connective tissue disorders caused by genetic variants in extracellular matrix genes such as Marfan syndrome. Mice with Fibrillin 1 gene variant Fbn1 C1039G/+ recapitulate histopathological features of Marfan syndrome. However, the cell heterogeneity and changes of gene expression at single cell level in Marfan syndrome valves are completed unknown.

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Cellular composition of murine mitral valves during autoimmune valvular carditis

Project description:To characterize the cell types that compose the mitral valve during the development of autoimmune valvular carditis, we utilized scRNA sequencing. Live cells from inflamed valves of K/B.g7 mice or uninflamed B.g7 controls were collected and analyzed at 3-, 8-, and 25 weeks of age.

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Differential Requirement for DICER1 Activity during the Development of Mitral and Tricuspid Vlaves

Project description:Mitral and tricuspid valves are essential for unidirectional blood flow in the heart. They are derived from similar cell sources, and yet congenital dysplasia affecting both valves is clinically rare, suggesting the presence of differential regulatory mechanisms underlying their development. We specifically inactivated Dicer1 in the endocardium during cardiogenesis and found that Dicer1-deletion caused congenital mitral valve stenosis and regurgitation, while it had no impact on other valves. We showed that hyperplastic mitral valves were caused by abnormal condensation and extracellular matrix (ECM) remodeling. Our single-cell RNA Sequencing analysis revealed impaired maturation of mesenchymal cells and abnormal expression of ECM genes in mutant mitral valves. Furthermore, expression of a set of miRNAs that target ECM genes was significantly lower in tricuspid valves compared to mitral valves, consistent with the idea that the miRNAs are differentially required for mitral and tricuspid valve development. We thus reveal miRNA-mediated gene regulation as a novel molecular mechanism that differentially regulates mitral and tricuspid valve development, thereby enhancing our understanding of the non-association of inborn mitral and tricuspid dysplasia observed clinically.

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Cellular composition of murine mitral valves during autoimmune valvular carditis

Project description:Cellular composition of murine mitral valves during autoimmune valvular carditis

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Gene expression profile at single cell level from mitral valves of wild-type and Fbn1 C1039G/+ mice at 1 month-of-age

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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)

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CCR2+ vs. CCR2- murine hematopoietic stem cells

Project description:Comparative analysis of FACS-sorted CCR2- and CCR2+ HSC in the steady state. CCR2+ HSC have fourfold higher proliferative rates than CCR2- HSC, are are biased towards the myeloid lineage and dominate the migratory HSC population. Comparison of pooled CCR2- and CCR2+ HSC (bone marrow from 20 mice pooled for each sample), three biological replicates each.

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