Biological implications of cell fusion

Key Points

  • Fusion of one or more cells can occur during development as well as in mature individuals. Fusion of two or more cells of the same type yields a syncytium. Syncytia are commonly found in placenta, bone, cartilage, muscle and multi-nucleated giant cells.

  • Fusion of two or more cells of different types can yield multi-nucleated cells called heterokaryons. Heterokaryons have been observed after cells of bone marrow origin fused with hepatocytes, cardiomyocytes and Purkinje neurons to form multi-nucleated cells.

  • Fusion of two or more cells of the same or different type and fusion of nuclei can yield synkaryons. Synkaryons have been found among hepatocytes, kidney tubules and B cells.

  • Cell fusion can cause a change in the phenotype and/or the function of cells. Cell fusion could therefore explain transdifferentiation of committed somatic cells.

  • Cell fusion can reverse or repair injury to tissues. In this context, cell fusion facilitates the regeneration of tissues.

  • Cell fusion can promote the transmission of viruses. Fusion of cells of individuals of disparate species might explain the transmission of viruses between species and the genesis of new pathogens.

  • Cell fusion and nuclear fusion that occur in the formation of synkaryons can allow the re-sorting and recombination of chromosomal DNA. Fusion of nuclei of an immature cell, such as a stem cell, and a mature cell might generate proliferation and malignancy.

Abstract

Until recently, cells were thought to be integral and discrete components of tissues, and their state was determined by cell differentiation. However, under some conditions, stem cells or their progeny can fuse with cells of other types, mixing cytoplasmic and even genetic material of different (heterotypic) origins. The fusion of heterotypic cells could be of central importance for development, repair of tissues and the pathogenesis of disease.

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Figure 1: Cells derived by fusion.
Figure 2: The stalk-pore model of cell fusion.
Figure 3: Two methods to identify cell fusion as an antecedent event.
Figure 4: The karyotype of synkaryons formed in vivo.
Figure 5: Role of synkaryons in disease.

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Acknowledgements

Work in the authors' laboratory is supported by grants from the National Institutes of Health.

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DATABASES

Entrez Gene

ADAM1

ADAM2

ADAM12

Fah

Izumo

FURTHER INFORMATION

Jeffrey Platt's laboratory

Glossary

DIFFERENTIATION

The acquisition of 'mature' cellular characteristics, which can be connected with the acquisition of the cell's mature function. Differentiation can be terminal, which means that the cell adopts a different set of characteristics and will not proliferate.

HETEROKARYON

A cell formed by the fusion of two or more cells of different types and having two or more distinct nuclei.

SYNKARYON

A cell formed by the fusion of two or more cells and having one common nucleus, formed by nuclear fusion.

HYBRID CELL

A cell that arises from the fusion of two different cells.

STALK

A structure that is formed when a fusion protein from one cell interacts with a receptor on a neighbouring cell, and the attractive force exceeds the repulsive force caused by hydration.

PORE

A structure that is formed on completion of the fusion of cell membranes; the 'stalk' elongates to form a fusion pore.

FUSOGEN

A protein or molecule that directly mediates the merging of cell membranes (for example, polyethylene glycol and calcium).

OSTEOCLAST

A bone-tissue-resorbing cell that is formed by the fusion of mononuclear cell precursors to yield multinucleated cells. Osteoclasts contribute to bone development and homeostasis, including the formation of canals and cavities.

ADAM FAMILY

A group of transmembrane proteins that contains a disintegrin and metalloprotease domain. Proteins of the ADAM family can promote cell adhesion and/or catalyse proteolysis and might promote or enable cells to fuse.

PLOIDY

The number of single sets of chromosomes in a cell.

TROPHOBLAST

A cell from the outermost layer of cells of the blastocyst, constituting the interface between the foetus and the mother. Cells of the trophoblast (cytotrophoblast) ultimately fuse to form the syncytiotrophoblast of the placenta.

SYNCYTIUM

A cell containing two or more nuclei, usually having a large, continuous mass of cytoplasm. A syncytium is generally formed by fusion of two or more cells of the same type.

MATERNAL-FETAL BARRIER

The placenta allows the exchange of oxygen and nutrients but restricts the interchange of cells between the foetus and the mother's uterus.

TRANSDIFFERENTIATION

A change from one differentiated state of a cell to another. Transdifferentiation is thought to be rare and possibly limited to stem cells.

FISH

Fluorescence in situ hybridization. A technique in which one or more genes are located in chromosomes by hybridization of fluorescently labelled complementary DNA. FISH can be used to determine the number of copies of a specific sequence of DNA in a cell.

HAEMATOPOIETIC

Related to the blood or blood cells. Haematopoietic stem cells give rise to cells of the various lineages of the blood and have been found to fuse with cells from non-haematopoietic tissues.

PARENCHYMAL CELL

A cell that contributes to the essential structure and/or function of an organ, in contrast to stroma or blood vessels.

MYOTUBE

A developing fibre of skeletal muscle with a tubular appearance.

HEPATOCYTE

A parenchymal cell of the liver. Hepatocytes are the only cells in mature humans that can undergo mitosis without cytokinesis to form multinucleated cell masses.

MYELOMONOCYTIC CELL

An immature white blood cell of the granulocyte–monocyte–histiocyte lineage. These cells typically have cytoplasmic granules, a large horse-shoe-shaped nucleus and cell markers characteristic of immature myeloid cells. The term can refer to leukaemia cells exhibiting both myeloid and monocytic properties.

PORCINE ENDOGENOUS RETROVIRUS

A retrovirus in germline DNA that is dormant in normal pigs and exists as DNA copies in every cell.

ALLOPHENIC MICE

Tetraparental mice formed by the aggregation of blastocyst cells or cells from early embryos of two genetically pure lines of mice. The cell aggregates are implanted in the uterus of a foster mother.

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Ogle, B., Cascalho, M. & Platt, J. Biological implications of cell fusion. Nat Rev Mol Cell Biol 6, 567–575 (2005). https://doi.org/10.1038/nrm1678

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