Cell-Cell Communication and Gene Regulation of Stem Cell-Parenchymal Cell Fusion

Abstract

Cell fusion, a natural process occurring between similar or dissimilar cell types, often confers new or enhanced functionality, yet its impact on cellular communication and gene regulation remains poorly understood. Here, we used recent analytical frameworks to investigate accidental cell fusion between murine cardiomyocytes (mHL1) and murine mesenchymal stromal/stem cells (mMSC) leveraging previously published single-cell RNA sequencing data. After fusion, we observed a biased distribution of gene expression and acquired phenotypes in fused hybrids. Trajectory inference showed that hybrids with a more mMSC-like transcriptome diverged more significantly from parental cells relative to hybrids with a more mHL1-like transcriptome. We also observed dynamic changes in cell-cell communication, with early (Day 1) downregulation of Wnt signaling and Melanogenesis evolving into the upregulation of pathways like Endocrine resistance and Focal adhesion by Day 3. Notably, ECM (extracellular matrix)-receptor interactions were largely consistent whether annotation or unsupervised Clustree methods were used. Furthermore, our analysis indicated the emergence of various cancer-associated signaling mechanisms. Our findings highlight the remarkable plasticity of cellular identity following fusion and lay the groundwork for future research into the precise molecular mechanisms driving these transformations and the potential of cell fusion for generating novel cell types.