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Multi-omics data reveal the origin of cardiac myxoma

ABSTRACT: Cardiac myxoma, the most common primary cardiac tumor, presents significant challenges due to its heterogeneous cellular composition and poorly defined signaling mechanisms. In this study, we applied single-nucleus RNA sequencing (snRNA-seq) to cardiac myxoma and matched normal cardiac tissues to elucidate the tumor’s cellular origin and molecular characteristics. Our analysis provides strong evidence that myxomas arise from endothelial cells. Abnormal endothelial-to-mesenchymal transition (EndMT) contributes to the coexistence of endothelial and mesenchymal phenotypes, while activation of the MET-PTK2 signaling axis appears to drive tumor progression. Pseudotime trajectory analysis revealed dynamic transitions from endothelial-mesenchymal states to metabolically active phenotypes, uncovering distinct myxoma subtypes with potential therapeutic relevance. This study highlights the value of snRNA-seq in resolving the cellular heterogeneity of rare cardiac tumors and provides a molecular framework for developing personalized therapies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE305759 | GEO | 2025/08/18

REPOSITORIES: GEO

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Project description:Background : Poxviruses have been shown to be efficient vectors for the production of protective immune responses in host species but also in on host species. Myxoma virus belongs to poxviridae family. In order to evaluate the capacity of (MYXV) as a vaccine vector in ruminants, we invistigated its interactions with bone marrow-derived dendritic cells (BM-DC). DCs are the most potent antigen-presenting cells and play a crucial role during the priming and reactivation of antigen-specific immune responses . Following infection by a pathogen, the functional changes of DC are essential since priming and polarization of the immune response depend on these changes . Therefore a better understanding of the modifications in gene expression of proinflammatory cytokines, chemokines and stimulatory molecules expression may prove useful in predicting whether or not a vaccine vector will be effective. Moreover, it may help identifying modifications for improving its efficacy. Methodology/Principal Findings: We investigated in vitro the interactions between recombinant MYXV expressing GFP protein, SG33-GFP and ovine BM-DCs. To gain a global view of the gene remodelling induced by MYXV, we infected BM-DCs from three sheep with SG33-GFP at different multiplicity of infection (MOI) (0, 1, 3) during different time (0, 3, 8 hours). We measured the expression of 15K probes in BM-DCs after each kind of conditions with ovine Agilent microarrays. Furthermore, a selected number of genes were confirmed by RT-qPCR. MYXV infection induces a strong reprogramming of the cells leading to the expression of pro-inflammatory cytokines and mobilisation of type I IFN pathways, cellular death and features associated with the activation of the adaptive immune response. Conclusion/Significance: Microarray profiling of a poxvirus-DC interaction help to delineate some interesting features of a vector candidate in ovine, and pave the way for additional improvements of a promising platform. Keywords : Myxoma virus ; bone marrow-derived dendritic cells ; transcriptome ; sheep; vaccine 9 samples: 3 time points and 3 replicates of MOI=1

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Multi-omics data reveal the origin of cardiac myxoma

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