Fusion between cells of different organisms (i.e., xenogeneic hybrids) can occur, and for humans this may occur in the course of tissue transplantation, animal handling, and food production. Previous work shows that conferred advantages are rare in xenogeneic hybrids, whereas risks of cellular dysregulation are high. Here, we explore the transcriptome of individual xenogeneic hybrids of human mesenchymal stem cells and murine cardiomyocytes soon after fusion and ask whether the process is stochastic or involves conserved pathway activation. Toward this end, single-cell RNA sequencing was used to analyze the transcriptomes of hybrid cells with respect to the human and mouse genomes. Consistent with previous work, hybrids possessed a unique transcriptome distinct from either fusion partner but were dominated by the cardiomyocyte transcriptome. New in this work is the documentation that a few genes that were latent in both fusion partners were consistently expressed in hybrids. Specifically, human growth hormone 1, murine ribosomal protein S27, and murine ATP synthase H+ transporting, mitochondrial Fo complex subunit C2 were expressed in nearly all hybrids. The consistent activation of latent genes between hybrids suggests conserved signaling mechanisms that either cause or are the consequence of fusion of these 2 cell types and might serve as a target for limiting unwanted xenogeneic fusion in the future.—Yuan, C., Freeman, B. T., McArdle, T. J., Jung, J. P., Ogle, B. M. Conserved pathway activation following xenogeneic, heterotypic fusion. FASEB J. 33, 6767–6777 (2019). www.fasebj.org.
Bibliographical noteFunding Information:
The authors thank Dr. Peiman Hematti (University of Wisconsin?Madison) for the kind donation of pluripotent stem cell?derived mesenchymal stem cells. The authors also thank Joshua Bailer and John Garbe (University of Minnesota Super-computing Institute) for assistance in setting up single-cell RNA sequencing workflow analyses for multiple genomes. This study was funded by the U.S. National Institutes of Health, National Heart, Lung, and Blood Institute (Grant HL137204); University of Minnesota Genomics Center New Investigator Award (NSF-GRFP, 2010105691); Minnesota's Discover, Research, and Innovation Economy, University of Minnesota Informatics Institute Graduate Fellowship; and the Minnesota Stem Cell Institute. The authors declare no conflicts of interest.
- cell fusion
- human growth hormone
- mesenchymal stem cell