Hostname: page-component-586b7cd67f-2plfb Total loading time: 0 Render date: 2024-11-24T02:45:50.692Z Has data issue: false hasContentIssue false

Fate determination of adult human glial progenitor cells

Published online by Cambridge University Press:  07 October 2009

Fraser J. Sim
Affiliation:
Center for Translational Neuromedicine, and the Department of Neurology, University of Rochester Medical Center, Rochester, NY
Martha S. Windrem
Affiliation:
Center for Translational Neuromedicine, and the Department of Neurology, University of Rochester Medical Center, Rochester, NY
Steven A. Goldman*
Affiliation:
Center for Translational Neuromedicine, and the Department of Neurology, University of Rochester Medical Center, Rochester, NY
*
Correspondence should be addressed to: Steven A. Goldman, Department of Neurology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 645, Rochester, NY, USA phone: 14642 585-275-9588 email: [email protected]

Abstract

Glial progenitor cells (GPCs) comprise the most abundant population of progenitor cells in the adult human brain. They are responsible for central nervous system (CNS) remyelination, and likely contribute to the astrogliotic response to brain injury and degeneration as well. Adult human GPCs are biased to differentiate as oligodendrocytes and elaborate new myelin, and yet they retain multilineage plasticity, and can give rise to neurons as well as astrocytes and oligodendrocytes once removed from the adult parenchymal environment. GPCs retain strong mechanisms for cell-autonomous self-renewal, and yet both their phenotype and fate may be dictated by their microenvironment. Using the transcriptional profiles of acutely isolated GPCs, we have begun to understand the operative ligand–receptor interactions involved in these processes, and have identified several key signaling pathways by which adult human GPCs may be reliably instructed to either oligodendrocytic or astrocytic fate. In addition, we have noted significant differences between the expressed genes and dominant signaling pathways of fetal and adult human GPCs, as well as between rodent and human GPCs. The latter data in particular call into question therapeutic strategies predicated solely upon data obtained using rodents, while perhaps highlighting the extent to which evolution has been attended by the phylogenetic modification of glial phenotype and function.

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

Armstrong, R.C., Dorn, H.H., Kufta, C.V., Friedman, E. and Dubois-Dalcq, M.E. (1992) Pre-oligodendrocytes from adult human CNS. Journal of Neuroscience 12, 15381547.CrossRefGoogle ScholarPubMed
Arsenijevic, Y., Villemure, J.G., Brunet, J.F., Bloch, J.J., Deglon, N., Kostic, C. et al. (2001) Isolation of multipotent neural precursors residing in the cortex of the adult human brain. Experimental Neurology 170, 4862.CrossRefGoogle ScholarPubMed
Belachew, S., Chittajallu, R., Aguirre, A.A., Yuan, X., Kirby, M., Anderson, S. et al. (2003) Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons. Journal of Cell Biology 161, 169186.CrossRefGoogle ScholarPubMed
Ben-Hur, T. and Goldman, S.A. (2008) Prospects of cell therapy for disorders of myelin. Annals of the New York Academy of Sciences 1142, 218249.CrossRefGoogle ScholarPubMed
Bradbury, J. (2002) Time right for statin trials in multiple sclerosis. Lancet 360, 1483.CrossRefGoogle ScholarPubMed
Cahoy, J.D., Emery, B., Kaushal, A., Foo, L.C., Zamanian, J.L., Christopherson, K.S. et al. (2008) A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. Journal of Neuroscience 28, 264278.CrossRefGoogle Scholar
Dimou, L., Simon, C., Kirchhoff, F., Takebayashi, H. and Gotz, M. (2008) Progeny of Olig2-expressing progenitors in the gray and white matter of the adult mouse cerebral cortex. Journal of Neuroscience 28, 1043410442.CrossRefGoogle ScholarPubMed
ffrench-Constant, C. and Raff, M.C. (1986) Proliferating bipotential glial progenitor cells in adult rat optic nerve. Nature 319, 499502.CrossRefGoogle ScholarPubMed
Franklin, R.J. (2002) Why does remyelination fail in multiple sclerosis? Nature Reviews. Neuroscience 3, 705714.CrossRefGoogle ScholarPubMed
Gage, F.H. (2000) Mammalian neural stem cells. Science 287, 14331438.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Goldman, S. (2003) Glia as neural progenitor cells. Trends in Neuroscience 26, 590596.CrossRefGoogle ScholarPubMed
Goldman, S.A., Schanz, S. and Windrem, M.S. (2008) Stem cell-based strategies for treating pediatric disorders of myelin. Human Molecular Genetics 17, R76R83.CrossRefGoogle ScholarPubMed
Gross, R.E., Mehler, M.F., Mabie, P.C., Zang, Z., Santschi, L. and Kessler, J.A. (1996) Bone morphogenetic proteins promote astroglial lineage commitment by mammalian subventricular zone progenitor cells. Neuron 17, 595606.CrossRefGoogle ScholarPubMed
Hardy, R. and Reynolds, R. (1991) Proliferation and differentiation potential of rat forebrain oligodendroglial progenitors both in vitro and in vivo. Development 111, 10611080.CrossRefGoogle ScholarPubMed
He, P. and Shen, Y. (2009) Interruption of beta-catenin signaling reduces neurogenesis in Alzheimer's disease. Journal of Neuroscience 29, 65456557.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle Scholar
Hu, B.Y., Du, Z.W., Li, X.J., Ayala, M. and Zhang, S.C. (2009) Human oligodendrocytes from embryonic stem cells: conserved SHH signaling networks and divergent FGF effects. Development 136, 14431452.CrossRefGoogle ScholarPubMed
Inoue, I., Goto, S., Mizotani, K., Awata, T., Mastunaga, T., Kawai, S. et al. (2000) Lipophilic HMG-CoA reductase inhibitor has an anti-inflammatory effect: reduction of MRNA levels for interleukin-1beta, interleukin-6, cyclooxygenase-2, and p22phox by regulation of peroxisome proliferator-activated receptor alpha (PPARalpha) in primary endothelial cells. Life Science 67, 863876.CrossRefGoogle ScholarPubMed
Irizarry, R.A., Bolstad, B.M., Collin, F., Cope, L.M., Hobbs, B. and Speed, T.P. (2003) Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Research 31, e15.CrossRefGoogle ScholarPubMed
Keyoung, H.M. and Goldman, S.A. (2007) Glial progenitor cell-based repair of demyelinating neurological diseases. Neurosurgery Clinics of North America 18, 93104.CrossRefGoogle ScholarPubMed
Kim, S.Y. and Volsky, D.J. (2005) PAGE: parametric analysis of gene set enrichment. BMC Bioinformatics 6, 144.CrossRefGoogle ScholarPubMed
Kirschenbaum, B., Nedergaard, M., Preuss, A., Barami, K., Fraser, R.A. and Goldman, S.A. (1994) In vitro neuronal production and differentiation by precursor cells derived from the adult human forebrain. Cerebral Cortex 4, 576589.CrossRefGoogle ScholarPubMed
Klopfleisch, S., Merkler, D., Schmitz, M., Kloppner, S., Schedensack, M., Jeserich, G. et al. (2008) Negative impact of statins on oligodendrocytes and myelin formation in vitro and in vivo. Journal of Neuroscience 28, 1360913614.CrossRefGoogle ScholarPubMed
Kondo, T. and Raff, M. (2000) Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells. Science 289, 17541757.CrossRefGoogle ScholarPubMed
Lim, D.A., Tramontin, A.D., Trevejo, J.M., Herrera, D.G., Garcia-Verdugo, J.M. and Alvarez-Buylla, A. (2000) Noggin antagonizes BMP signaling to create a niche for adult neurogenesis. Neuron 28, 713726.CrossRefGoogle ScholarPubMed
Meng, K., Rodriguez-Pena, A., Dimitrov, T., Chen, W., Yamin, M., Noda, M. et al. (2000) Pleiotrophin signals increased tyrosine phosphorylation of beta beta-catenin through inactivation of the intrinsic catalytic activity of the receptor-type protein tyrosine phosphatase beta/zeta. Proceedings of the National Academy of Sciences of the U.S.A. 97, 26032608.CrossRefGoogle ScholarPubMed
Miron, V., Rajasekharan, S., Jarjour, A., Zamvil, S., Kennedy, T. and Antel, J. (2007) Simvastatin regulates oligodendroglial process dynamics and survival. Glia 55, 130143.CrossRefGoogle ScholarPubMed
Miron, V.E., Zehntner, S.P., Kuhlmann, T., Ludwin, S.K., Owens, T., Kennedy, T.E. et al. (2009) Statin therapy inhibits remyelination in the central nervous system. American Journal of Pathology 174, 18801890.CrossRefGoogle ScholarPubMed
Noble, M., Wren, D. and Wolswijk, G. (1992) The O-2A(adult) progenitor cell: a glial stem cell of the adult central nervous system. Seminars in Cell Biology 3, 413422.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Oberheim, N., Wang, X., Goldman, S. and Nedergaard, S.A. (2006) Astrocytic complexity distinguishes the human brain. Trends in Neurosciences 29, 110.CrossRefGoogle ScholarPubMed
Oberheim, N.A., Takano, T., Han, X., He, W., Lin, J.H., Wang, F. et al. (2009) Uniquely hominid features of adult human astrocytes. Journal of Neuroscience 29, 32763287.CrossRefGoogle ScholarPubMed
Palmer, T.D., Markakis, E.A., Willhoite, A.R., Safar, F. and Gage, F.H. (1999) Fibroblast growth factor-2 activates a latent neurogenic program in neural stem cells from diverse regions of the adult CNS. Journal of Neuroscience 19, 84878497.CrossRefGoogle ScholarPubMed
Pincus, D.W., Harrison-Restelli, C., Barry, J., Goodman, R.R., Fraser, R.A., Nedergaard, M. et al. (1997) In vitro neurogenesis by adult human epileptic temporal neocortex. Clinical Neurosurgery 44, 1725.Google ScholarPubMed
Raff, M.C., Miller, R.H. and Noble, M. (1983) A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium. Nature 303, 390396.CrossRefGoogle ScholarPubMed
Rawson, R.B. (2003) The SREBP pathway – insights from insigs and insects. Nature Reviews. Molecular Cell Biology 4, 631640.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.CrossRefGoogle ScholarPubMed
Saluja, I., Granneman, J.G. and Skoff, R.P. (2001) PPAR delta agonists stimulate oligodendrocyte differentiation in tissue culture. Glia 33, 191204.3.0.CO;2-M>CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Shen, S., Liu, A., Li, J., Wolubah, C. and Casaccia-Bonnefil, P. (2008a) Epigenetic memory loss in aging oligodendrocytes in the corpus callosum. Neurobiology of Aging 29, 452463.CrossRefGoogle ScholarPubMed
Shen, S., Sandoval, J., Swiss, V.A., Li, J., Dupree, J., Franklin, R.J. et al. (2008b) Age-dependent epigenetic control of differentiation inhibitors is critical for remyelination efficiency. Nature Neuroscience 11, 10241034.CrossRefGoogle ScholarPubMed
Sim, F.J. and Goldman, S.A. (2005) White matter progenitor cells reside in an oligodendrogenic niche. Ernst Schering Research Foundation Workshop 53, 6181.CrossRefGoogle Scholar
Sim, F.J., Lang, J.K., Ali, T.A., Roy, N.S., Vates, G.E., Pilcher, W.H. et al. (2008) Statin treatment of adult human glial progenitors induces PPAR gamma-mediated oligodendrocytic differentiation. Glia 56, 954962.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Smyth, G.K. (2004) Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Statistical Applications in Genetics and Molecular Biology 3, Article3, PMID: 16646809.CrossRefGoogle ScholarPubMed
Stanislaus, R., Pahan, K., Singh, A.K. and Singh, I. (1999) Amelioration of experimental allergic encephalomyelitis in Lewis rats by lovastatin. Neuroscience Letters 269, 7174.CrossRefGoogle ScholarPubMed
Subramanian, A., Tamayo, P., Mootha, V.K., Mukherjee, S., Ebert, B.L., Gillette, M.A. et al. (2005) Gene set enrichment analysis: A knowledge based approach for interpreting genome-wide expression profiles. Proceedings of the National Academy of Sciences of the U.S.A. 102, 1554515550.CrossRefGoogle ScholarPubMed
Talloen, W., Clevert, D.A., Hochreiter, S., Amaratunga, D., Bijnens, L., Kass, S. et al. (2007) I/NI-calls for the exclusion of non-informative genes: a highly effective filtering tool for microarray data. Bioinformatics 23, 28972902.CrossRefGoogle Scholar
Temple, S. and Raff, M.C. (1985) Differentiation of a bipotential glial progenitor cell in a single cell microculture. Nature 313, 223225.CrossRefGoogle Scholar
Vollmer, T., Key, L., Durkalski, V., Tyor, W., Corboy, J., Markovic-Plese, S. et al. (2004) Oral simvastatin treatment in relapsing-remitting multiple sclerosis. Lancet 363, 16071608.CrossRefGoogle ScholarPubMed
Weber, M., Prod'homme, T., Steinman, L. and Zamvil, L. (2005) Drug insight: using statins to treat neuroinflammatory disease. Nature Clinical Practice. Neurology 1, 106112.CrossRefGoogle ScholarPubMed
Windrem, M.S., 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.CrossRefGoogle ScholarPubMed
Windrem, M.S., Roy, N.S., Wang, J., Nunes, M., Benraiss, A., Goodman, R. et al. (2002) Progenitor cells derived from the adult human subcortical white matter disperse and differentiate as oligodendrocytes within demyelinated lesions of the rat brain. Journal of Neuroscience Research 69, 966975.CrossRefGoogle ScholarPubMed
Windrem, M.S., Schanz, S., 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 otherwsie lethally hypomyelinated shiverer mouse. Cell Stem Cell 2, 553565.CrossRefGoogle ScholarPubMed
Yamashima, T., Tonchev, A.B., Vachkov, I.H., Popivanova, B.K., Seki, T., Sawamoto, K. et al. (2004) Vascular adventitia generates neuronal progenitors in the monkey hippocampus after ischemia. Hippocampus 14, 861.CrossRefGoogle ScholarPubMed
Zhang, S.C., Ge, B. and Duncan, I.D. (1999) Adult brain retains the potential to generate oligodendroglial progenitors with extensive myelination capacity. Proceedings of the National Academy of Sciences of the U.S.A. 96, 40894094.CrossRefGoogle ScholarPubMed
Zhu, X., Bergles, D.E. and Nishiyama, A. (2008) NG2 cells generate both oligodendrocytes and gray matter astrocytes. Development 135, 145157.CrossRefGoogle ScholarPubMed