Atrial Myxomas Arise From Multipotent Myxoid Cardiac Stem Cells
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ABSTRACT:
PROVIDER: PRJEB36314 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR3829740_1.fastq.gz | Fastqsanger.gz | |||
| ERR3829740_2.fastq.gz | Fastqsanger.gz | |||
| ERR3829741_1.fastq.gz | Fastqsanger.gz | |||
| ERR3829741_2.fastq.gz | Fastqsanger.gz | |||
| ERR3829742_1.fastq.gz | Fastqsanger.gz |
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Project description:Atrial Myxomas Arise From Multipotent Myxoid Cardiac Stem Cells
| PRJEB36114 | ENA
Project description:Myxomas, the most common primary tumor of the heart, usually develop in the atria and consist of a myxoid matrix composed of an acid-mucopolysaccharide-rich stroma with polygonal stromal cells scattered throughout the matrix. These benign tumors, despite their rarity, are a research focus because of their clinical presentation and uncertain histogenesis. The objective of this study was to assess whether adult cardiac stem/progenitor cells (CSCs) give rise to myxoma stromal cells and secrete the typical myxoid matrix. 23 collected tumors showed the typical histological features of cardiac atrial myxoma with polygonal cells positive for the myxoma tumor-cell marker, calretinin, dispersed in an abundant myxoid matrix. We detected myxoma cells positive for c-kit (c-kitpos) but very rare Isl-1 positive cells. Most of these c-kitpos cells were lineage-committed CD45pos/CD31pos cells. However, c-kitpos /CD45neg/CD31neg cardiac myxoma cells expressed stemness and cardiac progenitor cell transcription factors. Some (<10%) of these c-kitpos/ CD45neg/CD31neg/ myxoma cells expressed also calretinin, representing myxoma stromal precursor cells. c-kitpos/CD45neg/CD31neg cardiac myxoma cells secrete in vitro chondroitin-6-sulfate and hyaluronic acid, composing the gelatinous matrix of cardiac myxoma in vivo. In vitro, c-kitpos/CD45neg/CD31neg myxoma cells have stem cell properties being clonogenic, self-renewing and sphere forming. On the other hand, they exhibited an abortive cardiac differentiation potential with significant changes in their mRNA and microRNA transcriptome compared to normal c-kitpos/CD45neg /CD31neg CSCs. Importantly, myxoma-derived CSCs seed human atrial myxoma in xenograft’s experiments in NOD/SCID mice. Thus, un-committed c-kitpos/CD45neg /CD31neg cells fulfill the criteria of myxoma stem cells in atrial myxoma. Myxomas appear to be the first CSC-related human cardiac disease.
2020-05-02 | E-MTAB-8642 | biostudies-arrayexpress
Project description:Myxomas, the most common primary tumor of the heart, usually develop in the atria and consist of a myxoid matrix composed of an acid-mucopolysaccharide-rich stroma with polygonal stromal cells scattered throughout the matrix. These benign tumors, despite their rarity, are a research focus because of their clinical presentation and uncertain histogenesis. The objective of this study was to assess whether adult cardiac stem/progenitor cells (CSCs) give rise to myxoma stromal cells and secrete the typical myxoid matrix. 23 collected tumors showed the typical histological features of cardiac atrial myxoma with polygonal cells positive for the myxoma tumor-cell marker, calretinin, dispersed in an abundant myxoid matrix. We detected myxoma cells positive for c-kit (c-kitpos) but very rare Isl-1 positive cells. Most of these c-kitpos cells were lineage-committed CD45pos/CD31pos cells. However, c-kitpos /CD45neg/CD31neg cardiac myxoma cells expressed stemness and cardiac progenitor cell transcription factors. Some (<10%) of these c-kitpos/ CD45neg/CD31neg/ myxoma cells expressed also calretinin, representing myxoma stromal precursor cells. c-kitpos/CD45neg/CD31neg cardiac myxoma cells secrete in vitro chondroitin-6-sulfate and hyaluronic acid, composing the gelatinous matrix of cardiac myxoma in vivo. In vitro, c-kitpos/CD45neg/CD31neg myxoma cells have stem cell properties being clonogenic, self-renewing and sphere forming. On the other hand, they exhibited an abortive cardiac differentiation potential with significant changes in their mRNA and microRNA transcriptome compared to normal c-kitpos/CD45neg /CD31neg CSCs. Importantly, myxoma-derived CSCs seed human atrial myxoma in xenograft’s experiments in NOD/SCID mice. Thus, un-committed c-kitpos/CD45neg /CD31neg cells fulfill the criteria of myxoma stem cells in atrial myxoma. Myxomas appear to be the first CSC-related human cardiac disease.
2020-04-01 | E-MTAB-8701 | biostudies-arrayexpress
Project description:Atrial Myxomas Arise From Multipotent Myxoid Cardiac Stem Cells
2020-07-15 | E-MTAB-8701 | ExpressionAtlas
Project description:AimsCardiac myxomas usually develop in the atria and consist of an acid-mucopolysaccharide-rich myxoid matrix with polygonal stromal cells scattered throughout. These human benign tumours are a valuable research model because of the rarity of cardiac tumours, their clinical presentation and uncertain origin. Here, we assessed whether multipotent cardiac stem/progenitor cells (CSCs) give rise to atrial myxoma tissue.Methods and resultsTwenty-three myxomas were collected and analysed for the presence of multipotent CSCs. We detected myxoma cells positive for c-kit (c-kitpos) but very rare Isl-1 positive cells. Most of the c-kitpos cells were blood lineage-committed CD45pos/CD31pos cells. However, c-kitpos/CD45neg/CD31neg cardiac myxoma cells expressed stemness and cardiac progenitor cell transcription factors. Approximately ≤10% of the c-kitpos/CD45neg/CD31neg myxoma cells also expressed calretinin, a characteristic of myxoma stromal cells. In vitro, the c-kitpos/CD45neg/CD31neg myxoma cells secrete chondroitin-6-sulfate and hyaluronic acid, which are the main components of gelatinous myxoma matrix in vivo. In vitro, c-kitpos/CD45neg/CD31neg myxoma cells have stem cell properties being clonogenic, self-renewing, and sphere forming while exhibiting an abortive cardiac differentiation potential. Myxoma-derived CSCs possess a mRNA and microRNA transcriptome overall similar to normal myocardium-derived c-kitpos/CD45neg/CD31negCSCs , yet showing a relatively small and relevant fraction of dysregulated mRNA/miRNAs (miR-126-3p and miR-335-5p, in particular). Importantly, myxoma-derived CSCs but not normal myocardium-derived CSCs, seed human myxoma tumours in xenograft's in immunodeficient NOD/SCID mice.ConclusionMyxoma-derived c-kitpos/CD45neg/CD31neg CSCs fulfill the criteria expected of atrial myxoma-initiating stem cells. The transcriptome of these cells indicates that they belong to or are derived from the same lineage as the atrial multipotent c-kitpos/CD45neg/CD31neg CSCs. Taken together the data presented here suggest that human myxomas could be the first-described CSC-related human heart disease.
| S-EPMC7735815 | biostudies-literature
Project description:Atrial fibrillation (AFib) and the risk of its lethal complications are worsened by atrial fibrosis. A recent study implicates osteopontin (encoded by Spp1) secreted by atrial TREM2+ macrophages in this fibrosis. Here, we show that silencing Spp1 in TREM2+ cardiac macrophages using an antibody-siRNA conjugate (ARC) reduces atrial fibrosis and suppresses AFib, thus offering a new immunotherapy for this common arrhythmia.
2024-09-12 | GSE272503 | GEO
Project description:Single-cell profile of atrial human fibroblasts in cardiac arrhythmia atrial fibrillation
| PRJNA624783 | ENA
Project description:Atrial fibrillation (AF), the most common cardiac arrhythmia, is a major contributor to population mortality and morbidity. The goal of this study is to explore molecular mechanisms of the AF-induced profibrotic remodelling in human atrial fibroblasts (ACFs). Specifically, we assessed single-cell transcriptome of cultured human ACFs treated with calcitonin(CT) or vehicle (from 6 individual patients) and of freshly-isolated ACFs from patients with AF (4 individual patients) vs controls (4 individual patients). We found that ACF transcriptome was unaltered by CT in cultured ACFs, and identified 5 transcriptional clusters with 23 differentially expressed transcripts in AF in freshly-ioslated ACFs.
2020-07-10 | GSE148504 | GEO
Project description:Atrial fibrillation (AF), the most common cardiac arrhythmia, is a major contributor to population mortality and morbidity. The goal of this study is to explore molecular mechanisms of the AF-induced profibrotic remodelling in human atrial fibroblasts (ACFs). Specifically, we assessed single-cell transcriptome of cultured human ACFs treated with calcitonin(CT) or vehicle (from 6 individual patients) and of freshly-isolated ACFs from patients with AF (4 individual patients) vs controls (4 individual patients) (SR). We found that ACF transcriptome was unaltered by CT in cultured ACFs, and identified 5 transcriptional clusters with 23 differentially expressed transcripts in AF in freshly-ioslated ACFs.
2020-07-10 | GSE148506 | GEO
Project description:How cells acquire their fate is a fundamental question in both developmental and regenerative biology. Multipotent progenitors undergo gradual cell fate restriction in response to temporal and positional cues from the microenvironment, the nature of which is far from being clear. In the case of the lymphatic system, venous endothelial cells are thought to give rise to lymphatic vessels, through a process of trans-differentiation. Upon expression of a set of transcription factors, venous cells acquire a lymphatic fate, and bud out to generate the lymphatic vasculature. In this work we challenge this view and show that while lymphatic endothelial cells (LECs) do arise in the Cardinal Vein (CV), they do so from a previously uncharacterized pool of multipotent angioblasts. Using lymphatic-specific transgenic zebrafish, in combination with endothelial photoconvertible reporters, and long-term live imaging, we demonstrate that these multipotent angioblasts can generate not only lymphatic, but also arterious, and venous fates. We further reveal that the underlying endoderm serves as a source of Wnt5b, which acts as a lymphatic inductive signal, promoting the angioblast-to-lymphatic transition. Moreover, Wnt5b induced lymphatic specification in human embryonic stem cells- derived vascular progenitors, suggesting that this process is evolutionary conserved. Our results uncover a novel mechanism of lymphatic vessel formation, whereby multipotent angioblasts and not venous endothelial cells give rise to the lymphatic endothelium, and provide the first characterization of their inductive niche. More broadly, our findings highlight the CV as a plastic and heterogeneous structure containing different cell populations, analogous to the hematopoietic niche in the aortic floor. Following Kaede photoconversion of dorsal or ventral halves of the PCV in Tg(fli1:gal4;uasKaede) embryos at 24 hpf, 6 embryos per group were used for FACS isolation of Kaede photconverted (red) ECs.
2015-05-21 | E-GEOD-65751 | biostudies-arrayexpress