Skip to main content
Log in

Characterization of three human oligodendroglial cell lines as a model to study oligodendrocyte injury: Morphology and oligodendrocyte-specific gene expression

  • Published:
Journal of Neurocytology

Abstract

Oligodendrocytes, the myelin-forming cells of the central nervous system, are the target of pathogenic immune responses in multiple sclerosis. Primary cultures of human oligodendrocytes have been used to unravel the cellular and molecular mechanisms of immune-mediated injury of oligodendrocytes. However, these studies are hampered by the limited availability of viable human brain tissue. The present study was aimed at comparing the morphological and biochemical characteristics of the human oligodendroglial cell lines HOG, MO3.13 and KG-1C. We have determined oligodendrocyte-associated features of these lines and analyzed the degree to which they can be used as a model of human oligodendrocytes arrested at specific developmental stages. The oligodendroglial cell lines all exhibited markers of immature oligodendrocytes, such as CNPase and GalC, but not the astrocytic marker GFAP. Differentiation could be induced in HOG and MO3.13 cells, as was seen through a decrease in proliferation, an increase in process extension without formation of myelin sheets and up-regulation of genes associated with mature oligodendrocytes such as MBP and MOG. Microarray analysis revealed the expression of MAG, MOBP and OMG genes in HOG cells. The KG-1C cells displayed poor growth characteristics in the recommended conditions. In conclusion, our data show that the oligodendroglial cell lines HOG and MO3.13 can be used as a model of human oligodendrocytes ‘arrested’ in an immature developmental stage. Culturing in appropriate medium can induce further differentiation of these cells. These cell lines can therefore be applied as a model to study immune-mediated injury of oligodendrocytes in relation to disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • ARRIBA ZERPA, G. A., SALEH, M. C., FERNANDEZ, P. M., GUILLOU, F., ESPINOSA DE LOS, M. A., DE VELLIS, J., ZAKIN, M. M. & BARON, B. (2000) Alternative splicing prevents transferrin secretion during differentiation of a human oligodendrocyte cell line. Journal of Neuroscience Research 61, 388–395.

    Google Scholar 

  • BARBARESE, E., BARRY, C., D'OCCHIO, C., EDGAR, S., AKOWITZ, A. & CARSON, J. H. (1988) Expression of myelin basic protein mRNA and polypeptides in mouse oligodendrocytes in culture: Differential regulation by genetic and epigenetic factors. Brain Research 467, 183–191.

    Google Scholar 

  • BARBARESE, E., BRAUN, P. E. & CARSON, J. H. (1977) Identification of prelarge and presmall basic proteins in mouse myelin and their structural relationship to large and small basic proteins. Proceedings of the National Academy of Sciences USA 74, 3360–3364.

    Google Scholar 

  • BARBARESE, E., CARSON, J. H. & BRAUN, P. E. (1978) Accumulation of the four myelin basic proteins in mouse brain during development. Journal of Neurochemistry 31, 779–782.

    Google Scholar 

  • BAUMANN, N. & PHAM-DINH, D. (2001) Biology of oligodendrocyte and myelin in the mammalian central nervous system. Physiological Reviews 81, 871–927.

    Google Scholar 

  • BUNTINX, M., GIELEN, E., AMELOOT, M., STEELS, P., RAUS, J. & STINISSEN, P. Cytokine induced cell death in oligodendroglial cell lines. Alterations in Gene Expression. Submitted for publication.

  • CAMPAGNONI, A. T. (1988) Molecular biology of myelin proteins from the central nervous system. Journal of Neurochemistry 51, 1–14.

    Google Scholar 

  • CAMPAGNONI, A. T., PRIBYL, T. M., CAMPAGNONI, C. W., KAMPF, K., AMUR-UMARJEE, S., LANDRY, C. F., HANDLEY, V. W., NEWMAN, S. L., GARBAY, B. & KITAMURA, K. (1993) Structure and developmental regulation of Golli-mbp, a 105-kilobase gene that encompasses the myelin basic protein gene and is expressed in cells in the oligodendrocyte lineage in the brain. Journal of Biological Chemistry 268, 4930–4938.

    Google Scholar 

  • ECCLESTON, P. A. & SILBERBERG, D. H. (1984) The differentiation of oligodendrocytes in a serum-free hormone-supplemented medium. Brain Research 318, 1–9.

    Google Scholar 

  • ESCOBAR CABRERA, O. E., ZAKIN, M. M., SOTO, E. F. & PASQUINI, J. M. (1997) Single intracranial injection of apotransferrin in young rats increases the expression of specific myelin protein mRNA. Journal of Neuroscience Research 47, 603–608.

    Google Scholar 

  • ESPINOSA DE LOS, M. A., CHIAPELLI, F., FISHER, R. S. & DE VELLIS, J. (1988) Transferrin: An early marker of oligodendrocytes in culture. International Journal of Developmental Neuroscience 6, 167–175.

    Google Scholar 

  • GIVOGRI, M. I., BONGARZONE, E. R., SCHONMANN, V. & CAMPAGNONI, A. T. (2001) Expression and regulation of golli products of myelin basic protein gene during in vitro development of oligodendrocytes. Journal of Neuroscience Research 66, 679–690.

    Google Scholar 

  • KAMHOLZ, J., DE FERRA, F., PUCKETT, C. & LAZZARINI, R. (1986) Identification of three forms of humanmyelin basic protein bycDNAcloning. Proceeding of the National Academy of Sciences USA 83, 4962–4966.

    Google Scholar 

  • KAMHOLZ, J., TOFFENETTI, J. & LAZZARINI, R. A. (1988) Organization and expression of the human myelin basic protein gene. Journal of Neuroscience Research 21, 62–70.

    Google Scholar 

  • KASHIMA, T., TIU, S. N., MERRILL, J. E., VINTERS, H. V., DAWSON, G. & CAMPAGNONI, A. T. (1993) Expression of oligodendrocyte-associated genes in cell lines derived from human gliomas and neuroblastomas. Cancer Research 53, 170–175.

    Google Scholar 

  • KURIHARA, H., ZAMA, A., TAMURA, M., TAKEDA, J., SASAKI, T. & TAKEUCHI, T. (2000) Glioma/ glioblastoma-specific adenoviral gene expression using the nestin gene regulator. Gene Therapy 7, 686–693.

    Google Scholar 

  • LANDRY, C. F., ELLISON, J. A., PRIBYL, T. M., CAMPAGNONI, C., KAMPF, K. & CAMPAGNONI, A. T. (1996) Myelin basic protein gene expression in neurons: Developmental and regional changes in protein targeting within neuronal nuclei, cell bodies, and processes. Journal of Neuroscience 16, 2452–2462.

    Google Scholar 

  • LENDAHL, U., ZIMMERMAN, L. B. & MCKAY, R. D. (1990) CNS stem cells express a new class of intermediate filament protein. Cell 60, 585–595.

    Google Scholar 

  • MARTENSON, R. E. (1986) Possible hydrophobic region in myelin basic protein consisting of an orthogonally packed beta-sheet. Journal of Neurochemistry 46, 1612–1622.

    Google Scholar 

  • MCLAURIN, J., TRUDEL, G. C., SHAW, I. T., ANTEL, J. P. & CASHMAN, N. R. (1995)Ahumanglial hybrid cell line differentially expressing genes subserving oligodendrocyte and astrocyte phenotype. Journal of Neurobiology 26, 283–293.

    Google Scholar 

  • MIYAKE, E. (1979) Establishment of a human oligodendroglial cell line. Acta Neuropathologica (Berl) 46, 51–55.

    Google Scholar 

  • PEDRAZA, L. (1997) Nuclear transport of myelin basic protein. Journal of Neuroscience Research 50, 258–264.

    Google Scholar 

  • PEDRAZA, L., FIDLER, L., STAUGAITIS, S. M. & COLMAN, D. R. (1997) The active transport of myelin basic protein into the nucleus suggests a regulatory role in myelination. Neuron 18, 579–589.

    Google Scholar 

  • PHAM-DINH, D., DELLA, G. B., KERLERO, D. R. & DAUTIGNY, A. (1995) Structure of the human myelin/oligodendrocyte glycoprotein gene and multiple alternative spliced isoforms. Genomics 29, 345–352.

    Google Scholar 

  • POST, G. R. & DAWSON, G. (1992) Characterization of a cell line derived from a human oligodendroglioma. Molecular and Chemical Neuropathology 16, 303–317.

    Google Scholar 

  • PRIBYL, T. M., CAMPAGNONI, C. W., KAMPF, K., ELLISON, J. A., LANDRY, C. F., KASHIMA, T., McMAHON, J. & CAMPAGNONI, A. T. (1996) Expression of the myelin basic protein gene locus in neurons and oligodendrocytes in the human fetal central nervous system. Journal of Comparative Neurology 374, 342–353.

    Google Scholar 

  • PRIBYL, T. M., CAMPAGNONI, C. W., KAMPF, K., KASHIMA, T., HANDLEY, V. W., MCMAHON, J. & CAMPAGNONI, A. T. (1993) The human myelin basic protein gene is included within a 179-kilobase transcription unit: Expression in the immune and central nervous systems. Proceedings of the National Academy of Sciences USA 90, 10695–10699.

    Google Scholar 

  • PUSKÁS, L. G., ZVARA, A., HACKLER, L. JR. & VAN HUMMELEN, P. (2002) RNA amplification results in reproducible microarray data with slight ratio biases. Biotechniques 32, 1330–1334, 1336, 1338, 1340.

    Google Scholar 

  • ROTH, H. J., KRONQUIST, K. E., KERLERO, D. R., CRANDALL, B. F. & CAMPAGNONI, A. T. (1987) Evidence for the expression of four myelin basic protein variants in the developing human spinal cord through cDNA cloning. Journal of Neuroscience Research 17, 321–328.

    Google Scholar 

  • STREICHER, R. & STOFFEL, W. (1989) The organization of the human myelin basic protein gene. Comparison with the mouse gene. Biol Chem Hoppe Seyler 370, 503–510.

    Google Scholar 

  • SZUCHET, S., POLAK, P. E. & YIM, S. H. (1986) Mature oligodendrocytes cultured in the absence of neurons recapitulate the ontogenic development of myelin membranes. Developmental Neuroscience 8, 208–221.

    Google Scholar 

  • WANG, K. C., KOPRIVICA, V., KIM, J. A., SIVASANKARAN, R., GUO, Y., NEVE, R. L. & HE, Z. (2002) Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth. Nature 417, 941–944.

    Google Scholar 

  • YAMAMOTO, Y., MIZUNO, R., NISHIMURA, T., OGAWA, Y., YOSHIKAWA, H., FUJIMURA, H., ADACHI, E., KISHIMOTO, T., YANAGIHARA, T. & SAKODA, S. (1994) Cloning and expression of myelinassociated oligodendrocytic basic protein. A novel basic protein constituting the central nervous system myelin. Journal of Biological Chemistry 269, 31725–31730.

    Google Scholar 

  • YONG, V. & ANTEL, J. P. (1992) Culture of glial cells from human brain biopsies. In Protocols for Neural Cell Culture (edited by FEDOROFF, S. & RICHARDSON, A.) pp. 81–96. New York: Humana Press.

    Google Scholar 

  • ZIMMERMAN, L., PARR, B., LENDAHL, U., CUNNINGHAM, M., McKAY, R., GAVIN, B., MANN, J., VASSILEVA, G. & McMAHON, A. (1994) Independent regulatory elements in the nestin gene direct transgene expression to neural stem cells or muscle precursors. Neuron 12, 11–24.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Buntinx, M., Vanderlocht, J., Hellings, N. et al. Characterization of three human oligodendroglial cell lines as a model to study oligodendrocyte injury: Morphology and oligodendrocyte-specific gene expression. J Neurocytol 32, 25–38 (2003). https://doi.org/10.1023/A:1027324230923

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1027324230923

Keywords

Navigation