Single-cell RNA-seq reveals activation of unique gene groups as a consequence of stem cell-parenchymal cell fusion

Brian T. Freeman, Jangwook P. Jung, Brenda M. Ogle

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Fusion of donor mesenchymal stem cells with parenchymal cells of the recipient can occur in the brain, liver, intestine and heart following transplantation. The therapeutic benefit or detriment of resultant hybrids is unknown. Here we sought a global view of phenotypic diversification of mesenchymal stem cell-cardiomyocyte hybrids and associated time course. Using single-cell RNA-seq, we found hybrids consistently increase ribosome components and decrease genes associated with the cell cycle suggesting an increase in protein production and decrease in proliferation to accommodate the fused state. But in the case of most other gene groups, hybrids were individually distinct. In fact, though hybrids can express a transcriptome similar to individual fusion partners, approximately one-third acquired distinct expression profiles in a single day. Some hybrids underwent reprogramming, expressing pluripotency and cardiac precursor genes latent in parental cells and associated with developmental and morphogenic gene groups. Other hybrids expressed genes associated with ontologic cancer sets and two hybrids of separate experimental replicates clustered with breast cancer cells, expressing critical oncogenes and lacking tumor suppressor genes. Rapid transcriptional diversification of this type garners consideration in the context of cellular transplantation to damaged tissues, those with viral infection or other microenvironmental conditions that might promote fusion.

Original languageEnglish (US)
Article number23270
JournalScientific reports
Volume6
DOIs
StatePublished - Mar 21 2016

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Cell Fusion
Transcriptional Activation
Stem Cells
RNA
Mesenchymal Stromal Cells
Genes
Gene Components
Developmental Genes
Virus Diseases
Heart Transplantation
Tumor Suppressor Genes
Ribosomes
Oncogenes
Transcriptome
Cardiac Myocytes
Intestines
Cell Cycle
Transplantation
Breast Neoplasms
Liver

Cite this

Single-cell RNA-seq reveals activation of unique gene groups as a consequence of stem cell-parenchymal cell fusion. / Freeman, Brian T.; Jung, Jangwook P.; Ogle, Brenda M.

In: Scientific reports, Vol. 6, 23270, 21.03.2016.

Research output: Contribution to journalArticle

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