Hostname: page-component-586b7cd67f-t7fkt Total loading time: 0 Render date: 2024-11-26T22:10:08.601Z Has data issue: false hasContentIssue false

NG2-positive glia in the human central nervous system

Published online by Cambridge University Press:  29 September 2009

Susan M. Staugaitis
Affiliation:
Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH, USA
Bruce D. Trapp*
Affiliation:
Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
*
Correspondence should be addressed to: Bruce D. Trapp, Department of Neurosciences, Cleveland Clinic, 9500 Euclid Avenue NC30, Cleveland OH 44195, USA phone: 216-444-7177 fax: 216-444-7927 email: [email protected]

Abstract

Cells that express the NG2 chondroitin sulfate proteoglycan and platelet-derived growth factor receptor alpha (NG2 glia) are widespread in the adult human cerebral cortex and white matter and represent 10–15% of non-neuronal cells. The morphology and distribution of NG2 glia are similar to, but distinct from, both microglia and astrocytes. They are present as early as 17 weeks gestation and persist throughout life. NG2 glia can be detected in a variety of human central nervous system (CNS) diseases, of which multiple sclerosis is the best studied. NG2 glia show morphological changes in the presence of pathology and can show expression of the Ki-67 proliferation antigen. The antigenic profile and morphology of NG2 glia in human tissues are consistent with an oligodendrocyte progenitor function that has been well established in rodent models. Most antibodies to NG2 do not stain formalin-fixed paraffin-embedded tissues. Advances in our understanding of NG2 glia in human tissues will require the development of more robust markers for their detection in routinely processed human specimens.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Aguirre, A. and Gallo, V. (2004) Postnatal neurogenesis and gliogenesis in the olfactory bulb from NG2-expressing progenitors of the subventricular zone. Journal of Neuroscience 24, 1053010541.CrossRefGoogle ScholarPubMed
Back, S.A., Luo, N.L., Borenstein, N.S., Levine, J.M., Volpe, J.J. and Kinney, H.C. (2001) Late oligodendrocyte progenitors coincide with the developmental window of vulnerability for human perinatal white matter injury. Journal of Neuroscience 21, 13021312.CrossRefGoogle ScholarPubMed
Bailey, P. and Cushing, H. (1926) A Classification of Tumors of the Glioma Group on a Histogenesis Basis With a Correlated Study of Prognosis. Philadelphia: Lippincott.Google Scholar
Baracskay, K.L., Kidd, G.J., Miller, R.H. and Trapp, B.D. (2007) NG2-positive cells generate A2B5-positive oligodendrocyte precursor cells. Glia 55, 10011010.CrossRefGoogle ScholarPubMed
Bergles, D.E., Roberts, J.D., Somogyi, P. and Jahr, C.E. (2000) Glutamatergic synapses on oligodendrocyte precursor cells in the hippocampus. Nature 405, 187191.CrossRefGoogle ScholarPubMed
Bu, J., Akhtar, N. and Nishiyama, A. (2001) Transient expression of the NG2 proteoglycan by a subpopulation of activated macrophages in an excitotoxic hippocampal lesion. Glia 34, 296310.CrossRefGoogle Scholar
Bullwinkel, J., Baron-Luhr, B., Ludemann, A., Wohlenberg, C., Gerdes, J. and Scholzen, T. (2006) Ki-67 protein is associated with ribosomal RNA transcription in quiescent and proliferating cells. Journal of Cell Physiology 206, 624635.Google Scholar
Bumol, T.F. and Reisfeld, R.A. (1982) Unique glycoprotein–proteoglycan complex defined by monoclonal antibody on human melanoma cells. Proceedings of the National Academy of Sciences of the U.S.A. 79, 12451249.CrossRefGoogle ScholarPubMed
Butt, A.M., Kiff, J., Hubbard, P. and Berry, M. (2002) Synantocytes: new functions for novel NG2 expressing glia. Journal of Neurocytology 31, 551565.Google Scholar
Butt, A.M. and Nishiyama, A. (2002) Editorial. Journal of Neurocytology 31, 421422.CrossRefGoogle Scholar
Canoll, P. and Goldman, J.E. (2008) The interface between glial progenitors and gliomas. Acta Neuropathologica 116, 465477.CrossRefGoogle ScholarPubMed
Chang, A., Nishiyama, A., Peterson, J., Prineas, J. and Trapp, B.D. (2000) NG2-positive oligodendrocyte progenitor cells in adult human brain and multiple sclerosis lesions. Journal of Neuroscience 20, 64046412.CrossRefGoogle ScholarPubMed
Chang, A., Tourtellotte, W.W., Rudick, R. and Trapp, B.D. (2002) Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis. New England Journal of Medicine 346, 165173.CrossRefGoogle ScholarPubMed
Filipovic, R., Rakic, S. and Zecevic, N. (2002) Expression of Golli proteins in adult human brain and multiple sclerosis lesions. Journal of Neuroimmunology 127, 112.Google Scholar
Gogate, N., Verma, L., Zhou, J.M., Milward, E., Rusten, R., O'Connor, M. et al. (1994) Plasticity in the adult human oligodendrocyte lineage. Journal of Neuroscience 14, 45714587.Google Scholar
Graham, D.I. and Lantos, P.L. (2002) Greenfield's Neuropathology. London: A Hodder Arnold Publication.Google Scholar
He, W., Ingraham, C., Rising, L., Goderie, S. and Temple, S. (2001) Multipotent stem cells from the mouse basal forebrain contribute GABAergic neurons and oligodendrocytes to the cerebral cortex during embryogenesis. Journal of Neuroscience 21, 88548862.Google Scholar
Jakovcevski, I. and Zecevic, N. (2005) Sequence of oligodendrocyte development in the human fetal telencephalon. Glia 49, 480491.CrossRefGoogle ScholarPubMed
Ligon, K.L., Alberta, J.A., Kho, A.T., Weiss, J., Kwaan, M.R., Nutt, C.L. et al. (2004) The oligodendroglial lineage marker OLIG2 is universally expressed in diffuse gliomas. Journal of Neuropathology and Experimental Neurology 63, 499509.CrossRefGoogle ScholarPubMed
Lin, S.C. and Bergles, D.E. (2004) Synaptic signaling between neurons and glia. Glia 47, 290298.Google Scholar
Lin, S.C., Huck, J.H., Roberts, J.D., Macklin, W.B., Somogyi, P. and Bergles, D.E. (2005) Climbing fiber innervation of NG2-expressing glia in the mammalian cerebellum. Neuron 46, 773785.Google Scholar
Love, S., Louis, D. and Ellison, D. (2008) Greenfield's Neuropathology. London: Oxford University Press.Google Scholar
Maeda, Y., Solanky, M., Menonna, J., Chapin, J., Li, W. and Dowling, P. (2001) Platelet-derived growth factor-alpha receptor-positive oligodendroglia are frequent in multiple sclerosis lesions. Annals of Neurology 49, 776785.Google Scholar
Mallon, B.S., Shick, H.E., Kidd, G.J. and Macklin, W.B. (2002) Proteolipid promoter activity distinguishes two populations of NG2-positive cells throughout neonatal cortical development. Journal of Neuroscience 22, 876885.Google Scholar
Marshall, C.A. and Goldman, J.E. (2002) Subpallial dlx2-expressing cells give rise to astrocytes and oligodendrocytes in the cerebral cortex and white matter. Journal of Neuroscience 22, 98219830.CrossRefGoogle ScholarPubMed
McTigue, D.M., Wei, P. and Stokes, B.T. (2001) Proliferation of NG2-positive cells and altered oligodendrocyte numbers in the contused rat spinal cord. Journal of Neuroscience 21, 33923400.CrossRefGoogle ScholarPubMed
Miller, R.H., David, S., Patel, R., Abney, E.R. and Raff, M.C. (1985) A quantitative immunohistochemical study of macroglial cell development in the rat optic nerve: in vivo evidence for two distinct astrocyte lineages. Developmental Biology 111, 3541.Google Scholar
Miller, R.H. and Raff, M.C. (1984) Fibrous and protoplasmic astrocytes are biochemically and developmentally distinct. Journal of Neuroscience 4, 585592.CrossRefGoogle ScholarPubMed
Morgan, A.C. Jr., Galloway, D.R. and Reisfeld, R.A. (1981) Production and characterization of monoclonal antibody to a melanoma specific glycoprotein. Hybridoma 1, 2736.CrossRefGoogle ScholarPubMed
Nishiyama, A., Chang, A. and Trapp, B.D. (1999) NG2+ glial cells: a novel glial cell population in the adult brain. Journal of Neuropathology and Experimental Neurology 58, 11131121.Google Scholar
Nishiyama, A., Komitova, M., Suzuki, R. and Zhu, X. (2009) Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity. Nature Reviews. Neuroscience 10, 922.CrossRefGoogle ScholarPubMed
Nishiyama, A., Lin, X.H. and Stallcup, W.B. (1995) Generation of truncated forms of the NG2 proteoglycan by cell surface proteolysis. Molecular Biology of the Cell 6, 18191832.Google Scholar
Nunes, M.C., Roy, N.S., Keyoung, H.M., Goodman, R.R., McKhann, G., Jiang, L. et al. (2003) Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain. Nature Medicine 9, 439447.Google Scholar
Ozerdem, U., Grako, K.A., Dahlin-Huppe, K., Monosov, E. and Stallcup, W.B. (2001) NG2 proteoglycan is expressed exclusively by mural cells during vascular morphogenesis. Developmental Dynamics 222, 218227.CrossRefGoogle ScholarPubMed
Pluschke, G., Vanek, M., Evans, A., Dittmar, T., Schmid, P., Itin, P. et al. (1996) Molecular cloning of a human melanoma-associated chondroitin sulfate proteoglycan. Proceedings of the National Academy of Sciences of the U.S.A. 93, 97109715.CrossRefGoogle ScholarPubMed
Pouly, S., Becher, B., Blain, M. and Antel, J.P. (1999) Expression of a homologue of rat NG2 on human microglia. Glia 27, 259268.Google Scholar
Pouly, S., Prat, A., Blain, M., Olivier, A. and Antel, J. (2001) NG2 immunoreactivity on human brain endothelial cells. Acta Neuropathologica 102, 313320.CrossRefGoogle ScholarPubMed
Rakic, S. and Zecevic, N. (2003) Early oligodendrocyte progenitor cells in the human fetal telencephalon. Glia 41, 117127.Google Scholar
Reynolds, R., Dawson, M., Papadopoulos, D., Polito, A., DiBello, I., Pham-Dinh, D. et al. (2002) The response of NG2-expressing oligodendrocyte progenitors to demyelination in MOG-EAE and MS. Journal of Neurocytology 31, 523536.CrossRefGoogle ScholarPubMed
Rivers, L.E., Young, K.M., Rizzi, M., Jamen, F., Psachoulia, K., Wade, A. et al. (2008) PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice. Nature Neuroscience 11, 13921401.CrossRefGoogle ScholarPubMed
Roy, N.S., Wang, S., Harrison-Restelli, C., Benraiss, A., Fraser, R.A., Gravel, M. et al. (1999) Identification, isolation, and promoter-defined separation of mitotic oligodendrocyte progenitor cells from the adult human subcortical white matter. Journal of Neuroscience 19, 99869995.Google Scholar
Ruffini, F., Arbour, N., Blain, M., Olivier, A. and Antel, J.P. (2004) Distinctive properties of human adult brain-derived myelin progenitor cells. American Journal of Pathology 165, 21672175.Google Scholar
Sanai, N., Alvarez-Buylla, A. and Berger, M.S. (2005) Neural stem cells and the origin of gliomas. The New England Journal of Medicine 353, 811822.Google Scholar
Schrappe, M., Klier, F.G., Spiro, R.C., Waltz, T.A., Reisfeld, R.A. and Gladson, C.L. (1991) Correlation of chondroitin sulfate proteoglycan expression on proliferating brain capillary endothelial cells with the malignant phenotype of astroglial cells. Cancer Research 51, 49864993.Google Scholar
Scolding, N., Franklin, R., Stevens, S., Heldin, C.-H., Compston, A. and Newcombe, J. (1998) Oligodendrocyte progenitors are present in the normal adult human CNS and in the lesions of multiple sclerosis. Brain 121, 22212228.Google Scholar
Shoshan, Y., Nishiyama, A., Chang, A., Mork, S., Barnett, G.H., Cowell, J.K. et al. (1999) Expression of oligodendrocyte progenitor cell antigens by gliomas: implications for the histogenesis of brain tumors. Proceedings of the National Academy of Sciences of the U.S.A. 96, 1036110366.Google Scholar
Sim, F.J., Lang, J.K., Waldau, B., Roy, N.S., Schwartz, T.E., Pilcher, W.H. et al. (2006) Complementary patterns of gene expression by human oligodendrocyte progenitors and their environment predict determinants of progenitor maintenance and differentiation. Annals of Neurology 59, 763779.Google Scholar
Sosunov, A.A., Wu, X., Weiner, H.L., Mikell, C.B., Goodman, R.R., Crino, P.D. et al. (2008) Tuberous sclerosis: a primary pathology of astrocytes? Epilepsia 49 (Suppl 2), 5362.Google Scholar
Takei, H., Yogeswaren, S.T., Wong, K.K., Mehta, V., Chintagumpala, M., Dauser, R.C. et al. (2008) Expression of oligodendroglial differentiation markers in pilocytic astrocytomas identifies two clinical subsets and shows a significant correlation with proliferation index and progression free survival. Journal of Neurooncology 86, 183190.Google Scholar
Wigley, R., Hamilton, N., Nishiyama, A., Kirchhoff, F. and Butt, A.M. (2007) Morphological and physiological interactions of NG2-glia with astrocytes and neurons. Journal of Anatomy 210, 661670.Google Scholar
Wilson, H.C., Scolding, N.J. and Raine, C.S. (2006) Co-expression of PDGF alpha receptor and NG2 by oligodendrocyte precursors in human CNS and multiple sclerosis lesions. Journal of Neuroimmunology 176, 162173.Google Scholar
Windrem, M., Nunes, M.C., Rashbaum, W.K., Schwartz, T.H., Goodman, R.A., McKhann, G. et al. (2004) Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain. Nature Medicine 10, 9397.Google Scholar
Windrem, M.S., Schanz, S.J., Guo, M., Tian, G.F., Washco, V., Stanwood, N. et al. (2008) Neonatal chimerization with human glial progenitor cells can both remyelinate and rescue the otherwise lethally hypomyelinated shiverer mouse. Cell Stem Cell 2, 553565.Google Scholar
Wolswijk, G. (2002) Oligodendrocyte precursor cells in the demyelinated multiple sclerosis spinal cord. Brain 125, 338349.Google Scholar
Zhu, X., Bergles, D.E. and Nishiyama, A. (2008) NG2 cells generate both oligodendrocytes and gray matter astrocytes. Development 135, 145157.Google Scholar