4 results on '"Lavine K"'
Search Results
2. Spatial multi-omic map of human myocardial infarction.
- Author
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Kuppe C, Ramirez Flores RO, Li Z, Hayat S, Levinson RT, Liao X, Hannani MT, Tanevski J, Wünnemann F, Nagai JS, Halder M, Schumacher D, Menzel S, Schäfer G, Hoeft K, Cheng M, Ziegler S, Zhang X, Peisker F, Kaesler N, Saritas T, Xu Y, Kassner A, Gummert J, Morshuis M, Amrute J, Veltrop RJA, Boor P, Klingel K, Van Laake LW, Vink A, Hoogenboezem RM, Bindels EMJ, Schurgers L, Sattler S, Schapiro D, Schneider RK, Lavine K, Milting H, Costa IG, Saez-Rodriguez J, and Kramann R
- Subjects
- Case-Control Studies, Chromatin genetics, Epigenome, Humans, Myocardium metabolism, Myocardium pathology, Myocytes, Cardiac metabolism, Myocytes, Cardiac pathology, Time Factors, Atrial Remodeling genetics, Chromatin Assembly and Disassembly, Gene Expression Profiling, Myocardial Infarction genetics, Myocardial Infarction pathology, Single-Cell Analysis, Ventricular Remodeling genetics
- Abstract
Myocardial infarction is a leading cause of death worldwide
1 . Although advances have been made in acute treatment, an incomplete understanding of remodelling processes has limited the effectiveness of therapies to reduce late-stage mortality2 . Here we generate an integrative high-resolution map of human cardiac remodelling after myocardial infarction using single-cell gene expression, chromatin accessibility and spatial transcriptomic profiling of multiple physiological zones at distinct time points in myocardium from patients with myocardial infarction and controls. Multi-modal data integration enabled us to evaluate cardiac cell-type compositions at increased resolution, yielding insights into changes of the cardiac transcriptome and epigenome through the identification of distinct tissue structures of injury, repair and remodelling. We identified and validated disease-specific cardiac cell states of major cell types and analysed them in their spatial context, evaluating their dependency on other cell types. Our data elucidate the molecular principles of human myocardial tissue organization, recapitulating a gradual cardiomyocyte and myeloid continuum following ischaemic injury. In sum, our study provides an integrative molecular map of human myocardial infarction, represents an essential reference for the field and paves the way for advanced mechanistic and therapeutic studies of cardiac disease., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2022
- Full Text
- View/download PDF
3. Integrated multi-omic characterization of congenital heart disease.
- Author
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Hill MC, Kadow ZA, Long H, Morikawa Y, Martin TJ, Birks EJ, Campbell KS, Nerbonne J, Lavine K, Wadhwa L, Wang J, Turaga D, Adachi I, and Martin JF
- Subjects
- Bone Morphogenetic Protein Receptors metabolism, Cardiomyopathy, Dilated genetics, Cardiomyopathy, Dilated immunology, Cardiomyopathy, Dilated metabolism, Cardiomyopathy, Dilated pathology, Cardiomyopathy, Hypertrophic genetics, Cardiomyopathy, Hypertrophic immunology, Cardiomyopathy, Hypertrophic metabolism, Cardiomyopathy, Hypertrophic pathology, Disease Progression, Fibroblasts metabolism, Fibroblasts pathology, Forkhead Transcription Factors metabolism, Humans, Hypoplastic Left Heart Syndrome genetics, Hypoplastic Left Heart Syndrome immunology, Hypoplastic Left Heart Syndrome metabolism, Hypoplastic Left Heart Syndrome pathology, Image Cytometry, Insulin Resistance, Monocytes immunology, Myocytes, Cardiac metabolism, Myocytes, Cardiac pathology, RNA-Seq, Signal Transduction genetics, Single-Cell Analysis, Tetralogy of Fallot genetics, Tetralogy of Fallot immunology, Tetralogy of Fallot metabolism, Tetralogy of Fallot pathology, YAP-Signaling Proteins metabolism, Heart Defects, Congenital genetics, Heart Defects, Congenital immunology, Heart Defects, Congenital metabolism, Heart Defects, Congenital pathology, Phenotype
- Abstract
The heart, the first organ to develop in the embryo, undergoes complex morphogenesis that when defective results in congenital heart disease (CHD). With current therapies, more than 90% of patients with CHD survive into adulthood, but many suffer premature death from heart failure and non-cardiac causes
1 . Here, to gain insight into this disease progression, we performed single-nucleus RNA sequencing on 157,273 nuclei from control hearts and hearts from patients with CHD, including those with hypoplastic left heart syndrome (HLHS) and tetralogy of Fallot, two common forms of cyanotic CHD lesions, as well as dilated and hypertrophic cardiomyopathies. We observed CHD-specific cell states in cardiomyocytes, which showed evidence of insulin resistance and increased expression of genes associated with FOXO signalling and CRIM1. Cardiac fibroblasts in HLHS were enriched in a low-Hippo and high-YAP cell state characteristic of activated cardiac fibroblasts. Imaging mass cytometry uncovered a spatially resolved perivascular microenvironment consistent with an immunodeficient state in CHD. Peripheral immune cell profiling suggested deficient monocytic immunity in CHD, in agreement with the predilection in CHD to infection and cancer2 . Our comprehensive phenotyping of CHD provides a roadmap towards future personalized treatments for CHD., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2022
- Full Text
- View/download PDF
4. Role of transposable elements in heterochromatin and epigenetic control.
- Author
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Lippman Z, Gendrel AV, Black M, Vaughn MW, Dedhia N, McCombie WR, Lavine K, Mittal V, May B, Kasschau KD, Carrington JC, Doerge RW, Colot V, and Martienssen R
- Subjects
- Arabidopsis Proteins genetics, Chromosomes, Plant genetics, Cluster Analysis, DNA (Cytosine-5-)-Methyltransferases metabolism, DNA Methylation, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Genomic Imprinting, Homeodomain Proteins genetics, Oligonucleotide Array Sequence Analysis, RNA, Small Interfering genetics, RNA, Small Interfering metabolism, Tandem Repeat Sequences genetics, Transcription Factors genetics, Transcription Factors metabolism, Arabidopsis genetics, DNA Transposable Elements genetics, Epigenesis, Genetic genetics, Gene Expression Regulation, Plant, Heterochromatin genetics
- Abstract
Heterochromatin has been defined as deeply staining chromosomal material that remains condensed in interphase, whereas euchromatin undergoes de-condensation. Heterochromatin is found near centromeres and telomeres, but interstitial sites of heterochromatin (knobs) are common in plant genomes and were first described in maize. These regions are repetitive and late-replicating. In Drosophila, heterochromatin influences gene expression, a heterochromatin phenomenon called position effect variegation. Similarities between position effect variegation in Drosophila and gene silencing in maize mediated by "controlling elements" (that is, transposable elements) led in part to the proposal that heterochromatin is composed of transposable elements, and that such elements scattered throughout the genome might regulate development. Using microarray analysis, we show that heterochromatin in Arabidopsis is determined by transposable elements and related tandem repeats, under the control of the chromatin remodelling ATPase DDM1 (Decrease in DNA Methylation 1). Small interfering RNAs (siRNAs) correspond to these sequences, suggesting a role in guiding DDM1. We also show that transposable elements can regulate genes epigenetically, but only when inserted within or very close to them. This probably accounts for the regulation by DDM1 and the DNA methyltransferase MET1 of the euchromatic, imprinted gene FWA, as its promoter is provided by transposable-element-derived tandem repeats that are associated with siRNAs.
- Published
- 2004
- Full Text
- View/download PDF
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