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  • Review Article
  • Published:

Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity

Nature Reviews Neuroscience volume 10, pages 9–22 (2009)Cite this article

Key Points

  • NG2 cells, or polydendrocytes, are a population of CNS cells that are distinct from neurons, mature oligodendrocytes, astrocytes and microglia. They can be identified by the expression of the NG2 proteoglycan, have a highly branched morphology and are distributed throughout the grey and white matter.

  • Polydendrocytes differentiate into oligodendrocytes in vitro and have often been equated with oligodendrocyte precursor cells (OPCs). However, it is now highly debated whether polydendrocytes are multipotential cells that can give rise to neurons and astrocytes as well as oligodendrocytes. Recent findings from in vivo fate-mapping studies provide insights into this issue.

  • Polydendrocytes have an important role in remyelination, as they have the ability to proliferate and differentiate after a demyelinating insult.

  • Recent findings have described the interaction of polydendrocytes with neurons. These findings include observations that polydendrocytes receive synaptic inputs from neurons and the role of polydendrocytes in axonal growth.

Abstract

NG2 cells (also known as polydendrocytes) are a population of CNS cells that are distinct from neurons, mature oligodendrocytes, astrocytes and microglia. They can be identified by the expression of the proteoglycan NG2, have a highly branched morphology and are distributed throughout the grey and white matter. They differentiate into oligodendrocytes in vitro and have often been equated with oligodendrocyte precursor cells. However, whether polydendrocytes are multipotential cells that can give rise to neurons and astrocytes as well as oligodendrocytes is now highly debated. Furthermore, electrophysiological studies indicate that polydendrocytes receive synaptic input from neurons, suggesting that they are integrated in the neural network. This Review highlights recent findings and unresolved questions related to the lineage and function of polydendrocytes in the CNS.

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Figure 1: Development of polydendrocytes.
Figure 2: Hypothetical lineal relationship between polydendrocytes and other macroglia.
Figure 3: Events that occur in response to a demyelinating lesion in the corpus callosum.
Figure 4: Neuron–polydendrocyte synapses.

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Acknowledgements

The authors' work is funded by grants from the US National Institutes of Health, the National Science Foundation, the National Multiple Sclerosis Society, the Wadsworth Foundation and the Connecticut Stem Cell Research Program. The authors would like to thank B. Richardson, M. Gotz, L. Dimou and J. Trotter for sharing their unpublished results and helpful discussions.

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  1. Department of Physiology and Neurobiology, University of Connecticut, 75 North Eagleville Road, Storrs, Connecticut 062693156, USA. University of Connecticut Stem Cell Institute, University of Connecticut, Storrs, 06269-3156, Connecticut, USA

    Akiko Nishiyama, Mila Komitova, Ryusuke Suzuki & Xiaoqin Zhu

  2. University of Connecticut Stem Cell Institute, University of Connecticut, Storrs, 06269-3156, Connecticut, USA

    Akiko Nishiyama

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Glossary

Oligodendrocyte progenitor cell

(OPC). A committed cell that generates oligodendrocytes. The terms 'NG2 cell' and 'OPC' are often used synonymously. In this article, the term OPC is used for cells whose identity as NG2-expressing cells was not examined.

Pulse-chase labelling

A technique used to study the synthesis and trafficking of macromolecules in cells. A tracer compound (the pulse), such as 5-bromo-2′-deoxyuridine (BrdU), is given to cells or animals over a short period of time so that it is incorporated into the molecules or cells of interest. The cells or animals are then allowed to survive for a period of time in the absence of the tracer (the chase period), after which they are analysed for the distribution of the label.

Cre recombinase

A site-specific DNA recombinase from the P1 bacteriophage that excises DNA sequences flanked by Cre target sequences (loxP) that are in the same orientation.

Type-2 astrocyte

A GFAP+A2B5+ stellate cell that arises in culture from an A2B5+ O–2A progenitor cell.

Oligodendrocyte–type-2 astrocyte (O–2A) progenitor cell

An A2B5+ bipotential glial progenitor cell that can give rise to both oligodendrocytes and type-2 astrocytes in culture. The term is now used synonymously with the more frequently used term 'OPC'.

Type-1 astrocyte

A GFAP+ A2B5− flat cell in culture. It is morphologically and antigenically distinct from the type-2 astrocyte.

Glial-restricted progenitor (GRP) cell

An A2B5+ progenitor cell from the embryonic spinal cord that can give rise to type-1 and type-2 astrocytes and oligodendrocytes but not to neurons in culture.

Protoplasmic astrocyte

A type of astrocyte in the grey matter that has a large number of relatively short radially oriented processes with numerous spiny branches. The term is used for cells in vivo, but their relation to the type-1 and type-2 astrocytes that are seen in culture is not known.

Radial glial cell

A cell that appears during embryonic development, has its cell body in the ventricular zone and has a radially spanning thin process that reaches the pial surface. Neurons migrate along the radial processes of radial glia in the developing neocortex. Radial glia can generate neurons as well as astrocytes.

Retroviral labelling

A lineage-tracing experiment that uses a retrovirus that encodes a reporter. Because the retrovirus is an RNA virus with a genome that is integrated into the host genome, the virus is passed on to the progeny of the infected cells and is not diluted by cell division. The host cells must be proliferating to be infected by the retrovirus.

Fibrous astrocyte

An astrocyte in the white matter that was originally called a 'fibrous cell' because of its long thin processes. The term is used for cells in vivo, but their relation to the type-1 and type-2 astrocytes that are seen in culture is not known.

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Nishiyama, A., Komitova, M., Suzuki, R. et al. Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity. Nat Rev Neurosci 10, 9–22 (2009). https://doi.org/10.1038/nrn2495

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