Skip to main content
    • Aa
    • Aa
  • Get access
    Check if you have access via personal or institutional login
  • Cited by 17
  • Cited by
    This article has been cited by the following publications. This list is generated based on data provided by CrossRef.

    Dallérac, Glenn and Rouach, Nathalie 2016. Astrocytes as new targets to improve cognitive functions. Progress in Neurobiology,

    Dietz, Karen C. Polanco, Jessie J. Pol, Suyog U. and Sim, Fraser J. 2016. Targeting human oligodendrocyte progenitors for myelin repair. Experimental Neurology,

    Osorio, M. Joana and Goldman, Steven A. 2016. Glial progenitor cell-based treatment of the childhood leukodystrophies. Experimental Neurology,

    Chen, Xin Wang, Wei Zhang, Jianfang Li, Shiyong Zhao, Yilin Tan, Lei and Luo, Ailin 2015. Involvement of caspase-3/PTEN signaling pathway in isoflurane-induced decrease of self-renewal capacity of hippocampal neural precursor cells. Brain Research, Vol. 1625, p. 275.

    Goldman, Steven A. Nedergaard, Maiken and Windrem, Martha S. 2015. Modeling cognition and disease using human glial chimeric mice. Glia, Vol. 63, Issue. 8, p. 1483.

    Werneburg, Sebastian Buettner, Falk F.R. Mühlenhoff, Martina and Hildebrandt, Herbert 2015. Polysialic acid modification of the synaptic cell adhesion molecule SynCAM 1 in human embryonic stem cell-derived oligodendrocyte precursor cells. Stem Cell Research, Vol. 14, Issue. 3, p. 339.

    Zhou, Bo Osinski, Jason M. Mateo, Juan L. Martynoga, Ben Sim, Fraser J. Campbell, Christine E. Guillemot, Francois Piper, Michael and Gronostajski, Richard M. 2015. Loss of NFIX Transcription Factor Biases Postnatal Neural Stem/Progenitor Cells Toward Oligodendrogenesis. Stem Cells and Development, Vol. 24, Issue. 18, p. 2114.

    Boda, Enrica and Buffo, Annalisa 2014. Beyond cell replacement: unresolved roles of NG2-expressing progenitors. Frontiers in Neuroscience, Vol. 8,

    Goldman, Steven A and Osorio, Joana 2014. So many progenitors, so little myelin. Nature Neuroscience, Vol. 17, Issue. 4, p. 483.

    Swartling, Fredrik J. Bolin, Sara Phillips, Joanna J. and Persson, Anders I. 2014. Signals that regulate the oncogenic fate of neural stem cells and progenitors. Experimental Neurology, Vol. 260, p. 56.

    Wang, J. Pol, S. U. Haberman, A. K. Wang, C. O'Bara, M. A. and Sim, F. J. 2014. Transcription factor induction of human oligodendrocyte progenitor fate and differentiation. Proceedings of the National Academy of Sciences, Vol. 111, Issue. 28, p. E2885.

    Wang, Jing O'Bara, Melanie A. Pol, Suyog U. and Sim, Fraser J. 2013. CD133/CD140a-Based Isolation of Distinct Human Multipotent Neural Progenitor Cells and Oligodendrocyte Progenitor Cells. Stem Cells and Development, Vol. 22, Issue. 15, p. 2121.

    Conway, Gregory D. O'Bara, Melanie A. Vedia, Bansi H. Pol, Suyog U. and Sim, Fraser J. 2012. Histone deacetylase activity is required for human oligodendrocyte progenitor differentiation. Glia, Vol. 60, Issue. 12, p. 1944.

    Sanai, Nader 2011. Differential Expression of Neurofibromatosis 1 Among Discrete Postnatal Central Nervous System Progenitor Populations. World Neurosurgery, Vol. 75, Issue. 2, p. 181.

    Tzarouchi, L. C. Xydis, V. Zikou, A. K. Drougia, A. Astrakas, L. G. Papastefanaki, M. Andronikou, S. and Argyropoulou, Maria I. 2011. Diffuse periventricular leukomalacia in preterm children: assessment of grey matter changes by MRI. Pediatric Radiology, Vol. 41, Issue. 12, p. 1545.

    Cui, Qiao Ling Fragoso, Gabriela Miron, Veronique E. Darlington, Peter J. Mushynski, Walter E. Antel, Jack and Almazan, Guillermina 2010. Response of Human Oligodendrocyte Progenitors to Growth Factors and Axon Signals. Journal of Neuropathology & Experimental Neurology, Vol. 69, Issue. 9, p. 930.

    Richardson, William D. and Fields, R. Douglas 2009. Those enigmatic NG2 cells …. Neuron Glia Biology, Vol. 5, Issue. 1-2, p. 1.


Fate determination of adult human glial progenitor cells

  • Fraser J. Sim (a1), Martha S. Windrem (a1) and Steven A. Goldman (a1)
  • DOI:
  • Published online: 01 October 2009

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.

Corresponding author
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:
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

Y. Arsenijevic , J.G. Villemure , J.F. Brunet , J.J. Bloch , N. Deglon , C. Kostic (2001) Isolation of multipotent neural precursors residing in the cortex of the adult human brain. Experimental Neurology 170, 4862.

S. Belachew , R. Chittajallu , A.A. Aguirre , X. Yuan , M. Kirby , S. Anderson (2003) Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons. Journal of Cell Biology 161, 169186.

T. Ben-Hur and S.A. Goldman (2008) Prospects of cell therapy for disorders of myelin. Annals of the New York Academy of Sciences 1142, 218249.

J. Bradbury (2002) Time right for statin trials in multiple sclerosis. Lancet 360, 1483.

J.D. Cahoy , B. Emery , A. Kaushal , L.C. Foo , J.L. Zamanian , K.S. Christopherson (2008) A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. Journal of Neuroscience 28, 264278.

L. Dimou , C. Simon , F. Kirchhoff , H. Takebayashi and M. Gotz (2008) Progeny of Olig2-expressing progenitors in the gray and white matter of the adult mouse cerebral cortex. Journal of Neuroscience 28, 1043410442.

C. ffrench-Constant and M.C. Raff (1986) Proliferating bipotential glial progenitor cells in adult rat optic nerve. Nature 319, 499502.

R.J. Franklin (2002) Why does remyelination fail in multiple sclerosis? Nature Reviews. Neuroscience 3, 705714.

F.H. Gage (2000) Mammalian neural stem cells. Science 287, 14331438.

S.A. Goldman , S. Schanz and M.S. Windrem (2008) Stem cell-based strategies for treating pediatric disorders of myelin. Human Molecular Genetics 17, R76R83.

R.E. Gross , M.F. Mehler , P.C. Mabie , Z. Zang , L. Santschi and J.A. Kessler (1996) Bone morphogenetic proteins promote astroglial lineage commitment by mammalian subventricular zone progenitor cells. Neuron 17, 595606.

P. He and Y. Shen (2009) Interruption of beta-catenin signaling reduces neurogenesis in Alzheimer's disease. Journal of Neuroscience 29, 65456557.

B.Y. Hu , Z.W. Du , X.J. Li , M. Ayala and S.C. Zhang (2009) Human oligodendrocytes from embryonic stem cells: conserved SHH signaling networks and divergent FGF effects. Development 136, 14431452.

I. Inoue , S. Goto , K. Mizotani , T. Awata , T. Mastunaga , S. Kawai (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.

R.A. Irizarry , B.M. Bolstad , F. Collin , L.M. Cope , B. Hobbs and T.P. Speed (2003) Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Research 31, e15.

H.M. Keyoung and S.A. Goldman (2007) Glial progenitor cell-based repair of demyelinating neurological diseases. Neurosurgery Clinics of North America 18, 93104.

S.Y. Kim and D.J. Volsky (2005) PAGE: parametric analysis of gene set enrichment. BMC Bioinformatics 6, 144.

B. Kirschenbaum , M. Nedergaard , A. Preuss , K. Barami , R.A. Fraser and S.A. Goldman (1994) In vitro neuronal production and differentiation by precursor cells derived from the adult human forebrain. Cerebral Cortex 4, 576589.

S. Klopfleisch , D. Merkler , M. Schmitz , S. Kloppner , M. Schedensack , G. Jeserich (2008) Negative impact of statins on oligodendrocytes and myelin formation in vitro and in vivo. Journal of Neuroscience 28, 1360913614.

T. Kondo and M. Raff (2000) Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells. Science 289, 17541757.

D.A. Lim , A.D. Tramontin , J.M. Trevejo , D.G. Herrera , J.M. Garcia-Verdugo and A. Alvarez-Buylla (2000) Noggin antagonizes BMP signaling to create a niche for adult neurogenesis. Neuron 28, 713726.

K. Meng , A. Rodriguez-Pena , T. Dimitrov , W. Chen , M. Yamin , M. Noda (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.

V. Miron , S. Rajasekharan , A. Jarjour , S. Zamvil , T. Kennedy and J. Antel (2007) Simvastatin regulates oligodendroglial process dynamics and survival. Glia 55, 130143.

V.E. Miron , S.P. Zehntner , T. Kuhlmann , S.K. Ludwin , T. Owens , T.E. Kennedy (2009) Statin therapy inhibits remyelination in the central nervous system. American Journal of Pathology 174, 18801890.

M. Noble , D. Wren and G. Wolswijk (1992) The O-2A(adult) progenitor cell: a glial stem cell of the adult central nervous system. Seminars in Cell Biology 3, 413422.

M.C. Nunes , N.S. Roy , H.M. Keyoung , R.R. Goodman , G. McKhann , L. Jiang (2003) Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain. Nature Medicine 9, 439447.

N. Oberheim , X. Wang , S. Goldman and S.A. Nedergaard (2006) Astrocytic complexity distinguishes the human brain. Trends in Neurosciences 29, 110.

N.A. Oberheim , T. Takano , X. Han , W. He , J.H. Lin , F. Wang (2009) Uniquely hominid features of adult human astrocytes. Journal of Neuroscience 29, 32763287.

M.C. Raff , R.H. Miller and M. Noble (1983) A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium. Nature 303, 390396.

R.B. Rawson (2003) The SREBP pathway – insights from insigs and insects. Nature Reviews. Molecular Cell Biology 4, 631640.

L.E. Rivers , K.M. Young , M. Rizzi , F. Jamen , K. Psachoulia , A. Wade (2008) PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice. Nature Neuroscience 11, 13921401.

I. Saluja , J.G. Granneman and R.P. Skoff (2001) PPAR delta agonists stimulate oligodendrocyte differentiation in tissue culture. Glia 33, 191204.

N. Scolding , R. Franklin , S. Stevens , C.H. Heldin , A. Compston and J. Newcombe (1998) Oligodendrocyte progenitors are present in the normal adult human CNS and in the lesions of multiple sclerosis. Brain 121, 22212228.

S. Shen , A. Liu , J. Li , C. Wolubah and P. Casaccia-Bonnefil (2008a) Epigenetic memory loss in aging oligodendrocytes in the corpus callosum. Neurobiology of Aging 29, 452463.

S. Shen , J. Sandoval , V.A. Swiss , J. Li , J. Dupree , R.J. Franklin (2008b) Age-dependent epigenetic control of differentiation inhibitors is critical for remyelination efficiency. Nature Neuroscience 11, 10241034.

F.J. Sim and S.A. Goldman (2005) White matter progenitor cells reside in an oligodendrogenic niche. Ernst Schering Research Foundation Workshop 53, 6181.

F.J. Sim , J.K. Lang , T.A. Ali , N.S. Roy , G.E. Vates , W.H. Pilcher (2008) Statin treatment of adult human glial progenitors induces PPAR gamma-mediated oligodendrocytic differentiation. Glia 56, 954962.

F.J. Sim , J.K. Lang , B. Waldau , N.S. Roy , T.E. Schwartz , W.H. Pilcher (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.

G.K. Smyth (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.

R. Stanislaus , K. Pahan , A.K. Singh and I. Singh (1999) Amelioration of experimental allergic encephalomyelitis in Lewis rats by lovastatin. Neuroscience Letters 269, 7174.

W. Talloen , D.A. Clevert , S. Hochreiter , D. Amaratunga , L. Bijnens , S. Kass (2007) I/NI-calls for the exclusion of non-informative genes: a highly effective filtering tool for microarray data. Bioinformatics 23, 28972902.

S. Temple and M.C. Raff (1985) Differentiation of a bipotential glial progenitor cell in a single cell microculture. Nature 313, 223225.

T. Vollmer , L. Key , V. Durkalski , W. Tyor , J. Corboy , S. Markovic-Plese (2004) Oral simvastatin treatment in relapsing-remitting multiple sclerosis. Lancet 363, 16071608.

M. Weber , T. Prod'homme , L. Steinman and L. Zamvil (2005) Drug insight: using statins to treat neuroinflammatory disease. Nature Clinical Practice. Neurology 1, 106112.

M.S. Windrem , M.C. Nunes , W.K. Rashbaum , T.H. Schwartz , R.A. Goodman , G. McKhann (2004) Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain. Nature Medicine 10, 9397.

M.S. Windrem , N.S. Roy , J. Wang , M. Nunes , A. Benraiss , R. Goodman (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.

M.S. Windrem , S. Schanz , M. Guo , G.-F. Tian , V. Washco , N. Stanwood (2008) Neonatal chimerization with human glial progenitor cells can both remyelinate and rescue the otherwsie lethally hypomyelinated shiverer mouse. Cell Stem Cell 2, 553565.

T. Yamashima , A.B. Tonchev , I.H. Vachkov , B.K. Popivanova , T. Seki , K. Sawamoto (2004) Vascular adventitia generates neuronal progenitors in the monkey hippocampus after ischemia. Hippocampus 14, 861.

S.C. Zhang , B. Ge and I.D. Duncan (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.

X. Zhu , D.E. Bergles and A. Nishiyama (2008) NG2 cells generate both oligodendrocytes and gray matter astrocytes. Development 135, 145157.

S. Goldman (2003) Glia as neural progenitor cells. Trends in Neuroscience 26, 590596.

A. Subramanian , P. Tamayo , V.K. Mootha , S. Mukherjee , B.L. Ebert , M.A. Gillette (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.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Neuron Glia Biology
  • ISSN: 1740-925X
  • EISSN: 1741-0533
  • URL: /core/journals/neuron-glia-biology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *