Skip to main content
SpringerLink
Log in
Book cover

Endogenous Stem Cell-Based Brain Remodeling in Mammals pp 137–158Cite as

Regenerative Potential of NG2 Cells

  • Chapter
  • First Online:

  • 781 Accesses

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

Abstract

NG2 cells are a subtype of widely distributed glial cells representing around 5 % of the total number of cells in the mammalian central nervous system (CNS). NG2 cells are mostly known for their role as oligodendrocyte progenitor cells (OPCs) and have been shown to generate most if not all oligodendrocytes and myelin, both during development and after a demyelinating injury. It has also been proposed that NG2 cells could play additional roles in the brain, such as regulating axon growth and synapse formation or act as endogenous neural stem cells. The regenerative potential of NG2 cells is quite unique since they are not only able to regenerate themselves extensively through proliferation and migration in the adult brain but are also responsible for the remarkable ability of the adult central nervous system to fully regenerate myelin after a demyelinating injury. NG2 cells also exhibit some properties of neural stem cells and are able to generate neurons and astrocytes in vitro, although their neurogenic and gliogenic potential seem much more limited in vivo (6.3, the neurogenic and gliogenic potential of NG2 cells). Here, we review and discuss our current knowledge on the self-regenerative ability of NG2 cells, their role in oligodendrocyte regeneration, and their neurogenic and gliogenic potential.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

ALS:

Amyotrophic lateral sclerosis

AMPA:

2-Amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid

Ara-C:

Arabinofuranosyl cytidine

BAC:

Bacterial artificial chromosome

BMP:

Bone morphogenetic protein

BrdU:

5-Bromo-20-deoxyuridine

CNP:

2′,3′-Cyclic-nucleotide 3′-phosphodiesterase

CNS:

Central nervous system

ERK:

Extracellular signal-regulated kinase

FCS:

Fetal calf serum

FGF:

Fibroblast growth factor

FGFR:

Fibroblast growth factor receptor

GABA:

Gamma-aminobutyric acid

GalC:

Galactosylceramidase

HDAC:

Histone deacetylase

hIPSC:

Human induced pluripotent stem cells

MAG:

Myelin-associated glycoprotein

MBP:

Myelin basic protein

MOG:

Myelin oligodendrocyte glycoprotein

MS:

Multiple sclerosis

NG2:

Nerve/glial antigen-2

OPC:

Oligodendrocyte progenitor cell

PDGF:

Platelet-derived growth factor

PDGFR:

Platelet-derived growth factor receptor

PEDF:

Pigment epithelium-derived factor

PI3K:

Phosphatidylinositol-4,5-bisphosphate 3-kinase

PLP:

Myelin proteolipid protein

pMN:

Progenitor of motor neurons

Shh:

Sonic hedgehog

SVZ:

Subventricular zone

VZ:

Ventricular zone

References

  • Aguirre A, Gallo V (2004) Postnatal neurogenesis and gliogenesis in the olfactory bulb from NG2-expressing progenitors of the subventricular zone. J Neurosci 24:10530–10541

    CAS  PubMed  Google Scholar 

  • Aguirre A, Gallo V (2007) Reduced EGFR signaling in progenitor cells of the adult subventricular zone attenuates oligodendrogenesis after demyelination. Neuron Glia Biol 3:209–220

    PubMed Central  PubMed  Google Scholar 

  • Aguirre AA, Chittajallu R, Belachew S, Gallo V (2004) NG2-expressing cells in the subventricular zone are type C-like cells and contribute to interneuron generation in the postnatal hippocampus. J Cell Biol 165:575–589

    CAS  PubMed  Google Scholar 

  • Aguirre A, Dupree JL, Mangin JM, Gallo V (2007) A functional role for EGFR signaling in myelination and remyelination. Nat Neurosci 10:990–1002

    CAS  PubMed  Google Scholar 

  • Armstrong R, Friedrich VL Jr, Holmes KV, Dubois-Dalcq M (1990) In vitro analysis of the oligodendrocyte lineage in mice during demyelination and remyelination. J Cell Biol 111:1183–1195

    CAS  PubMed  Google Scholar 

  • Arnett HA, Fancy SP, Alberta JA, Zhao C, Plant SR, Kaing S, Raine CS, Rowitch DH, Franklin RJ, Stiles CD (2004) bHLH transcription factor Olig1 is required to repair demyelinated lesions in the CNS. Science 306:2111–2115

    CAS  PubMed  Google Scholar 

  • Assanah M, Lochhead R, Ogden A, Bruce J, Goldman J, Canoll P (2006) Glial progenitors in adult white matter are driven to form malignant gliomas by platelet-derived growth factor-expressing retroviruses. J Neurosci 26:6781–6790

    CAS  PubMed  Google Scholar 

  • Barres BA (2008) The mystery and magic of glia: a perspective on their roles in health and disease. Neuron 60(4):30–440

    Google Scholar 

  • Belachew S, Chittajallu R, Aguirre AA, Yuan X, Kirby M, Anderson S, Gallo V (2003) Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons. J Cell Biol 161:169–186

    CAS  PubMed  Google Scholar 

  • Bergles DE, Roberts JD, Somogyi P, Jahr CE (2000) Glutamatergic synapses on oligodendrocyte precursor cells in the hippocampus. Nature 405:187–191

    CAS  PubMed  Google Scholar 

  • Binamé F, Sakry D, Dimou L, Jolivel V, Trotter J (2013) NG2 regulates directional migration of oligodendrocyte precursor cells via Rho GTPases and polarity complex proteins. J Neurosci 33:10858–10874

    PubMed  Google Scholar 

  • Blackiston DJ, McLaughlin KA, Levin M (2009) Bioelectric controls of cell proliferation: ion channels, membrane voltage and the cell cycle. Cell Cycle 8:3519–3528

    PubMed Central  PubMed  Google Scholar 

  • Blakemore WF, Irvine KA (2008) Endogenous or exogenous oligodendrocytes for remyelination. J Neurol Sci 265:43–46

    CAS  PubMed  Google Scholar 

  • Bögler O, Wren D, Barnett SC, Land H, Noble M (1990) Cooperation between two growth factors promotes extended self-renewal and inhibits differentiation of oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells. Proc Natl Acad Sci U S A 87:6368–6372

    PubMed Central  PubMed  Google Scholar 

  • Bouslama-Oueghlani L, Wehrlé R, Sotelo C, Dusart I (2005) Heterogeneity of NG2-expressing cells in the newborn mouse cerebellum. Dev Biol 285:409–421

    CAS  PubMed  Google Scholar 

  • Bradl M, Lassmann H (2010) Oligodendrocytes: biology and pathology. Acta Neuropathol 119:37–53

    PubMed Central  PubMed  Google Scholar 

  • Briançon-Marjollet A, Balenci L, Fernandez M, Esteve F, Honnorat J, Farion R, Beaumont M, Barbier E, Remy C, Baudier J (2010) NG2-expressing glial precursor cells are a new potential oligodendroglioma cell initiating population in N-ethyl-N-nitrosourea-induced gliomagenesis. Carcinogenesis 31:1718–1725

    PubMed Central  PubMed  Google Scholar 

  • Cai J, Qi Y, Hu X, Tan M, Liu Z, Zhang J, Li Q, Sander M, Qiu M (2005) Generation of oligodendrocyte precursor cells from mouse dorsal spinal cord independent of Nkx6 regulation and Shh signaling. Neuron 45:41–53

    CAS  PubMed  Google Scholar 

  • Calver AR, Hall AC, Yu WP, Walsh FS, Heath JK, Betsholtz C, Richardson WD (1998) Oligodendrocyte population dynamics and the role of PDGF in vivo. Neuron 20:869–882

    CAS  PubMed  Google Scholar 

  • Carroll WM, Jennings AR (1994) Early recruitment of oligodendrocyte precursors in CNS remyelination. Brain 117:563–578

    PubMed  Google Scholar 

  • Cayre M, Canoll P, Goldman JE (2009) Cell migration in the normal and pathological postnatal mammalian brain. Prog Neurobiol 88:41–63

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chang A, Nishiyama A, Peterson J, Prineas J, Trapp BD (2000) NG2-positive oligodendrocyte progenitor cells in adult human brain and multiple sclerosis lesions. J Neurosci 20:6404–6412

    CAS  PubMed  Google Scholar 

  • Chang A, Tourtellotte WW, Rudick R, Trapp BD (2002) Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis. N Engl J Med 346:165–173

    PubMed  Google Scholar 

  • Chari DM, Blakemore WF (2002) Efficient recolonisation of progenitor-depleted areas of the CNS by adult oligodendrocyte progenitor cells. Glia 37:307–313

    PubMed  Google Scholar 

  • Chari DM, Gilson JM, Franklin RJ, Blakemore WF (2006) Oligodendrocyte progenitor cell transplantation is unlikely to offer a means of preventing X-irradiation induced damage in the CNS. Exp Neurol 198:145–153

    CAS  PubMed  Google Scholar 

  • Chew LJ, Gallo V (2009) The Yin and Yang of Sox proteins: activation and repression in development and disease. J Neurosci Res 87:3277–3287

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chittajallu R, Aguirre AA, Gallo V (2005) Downregulation of platelet-derived growth factor-alpha receptor-mediated tyrosine kinase activity as a cellular mechanism for K+-channel regulation during oligodendrocyte development in situ. J Neurosci 25:8601–8610

    CAS  PubMed  Google Scholar 

  • Chong SY, Chan JR (2010) Tapping into the glial reservoir: cells committed to remaining uncommitted. J Cell Biol 188:305–312

    CAS  PubMed  Google Scholar 

  • Chung SH, Guo F, Jiang P, Pleasure DE, Deng W (2013) Olig2/Plp-positive progenitor cells give rise to Bergmann glia in the cerebellum. Cell Death Dis 4:e546

    CAS  PubMed Central  PubMed  Google Scholar 

  • Clarke LE, Young KM, Hamilton NB, Li H, Richardson WD, Attwell D (2012) Properties and fate of oligodendrocyte progenitor cells in the corpus callosum, motor cortex, and piriform cortex of the mouse. J Neurosci 32:8173–8185

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dawson MR, Levine JM, Reynolds R (2000) NG2-expressing cells in the central nervous system: are they oligodendroglial progenitors? J Neurosci Res 61:471–479

    CAS  PubMed  Google Scholar 

  • Dawson MR, Polito A, Levine JM, Reynolds R (2003) NG2-expressing glial progenitor cells: an abundant and widespread population of cycling cells in the adult rat CNS. Mol Cell Neurosci 24:476–488

    CAS  PubMed  Google Scholar 

  • Dayer AG, Cleaver KM, Abouantoun T, Cameron HA (2005) New GABAergic interneurons in the adult neocortex and striatum are generated from different precursors. J Cell Biol 168:415–427

    CAS  PubMed  Google Scholar 

  • de Castro F, Bribián A (2005) The molecular orchestra of the migration of oligodendrocyte precursors during development. Brain Res Rev 49:227–241

    PubMed  Google Scholar 

  • Dimou L, Simon C, Kirchhoff F, Takebayashi H, Götz M (2008) Progeny of Olig2-expressing progenitors in the gray and white matter of the adult mouse cerebral cortex. J Neurosci 28:10434–10442

    CAS  PubMed  Google Scholar 

  • Ebner S, Dunbar M, McKinnon RD (2000) Distinct roles for PI3K in proliferation and survival of oligodendrocyte progenitor cells. J Neurosci Res 62:336–345

    CAS  PubMed  Google Scholar 

  • Edgar JM, Nave KA (2009) The role of CNS glia in preserving axon function. Curr Opin Neurobiol 19:498–504

    CAS  PubMed  Google Scholar 

  • Emery B, Agalliu D, Cahoy JD, Watkins TA, Dugas JC, Mulinyawe SB, Ibrahim A, Ligon KL, Rowitch DH, Barres BA (2009) Myelin gene regulatory factor is a critical transcriptional regulator required for CNS myelination. Cell 138:172–185

    CAS  PubMed Central  PubMed  Google Scholar 

  • Etxeberria A, Mangin JM, Aguirre A, Gallo V (2010) Adult-born SVZ progenitors receive transient synapses during remyelination in corpus callosum. Nat Neurosci 13:287–289

    CAS  PubMed  Google Scholar 

  • Fancy SP, Chan JR, Baranzini SE, Franklin RJ, Rowitch DH (2011) Myelin regeneration: a recapitulation of development? Annu Rev Neurosci 34:21–43

    CAS  PubMed  Google Scholar 

  • Fogarty M, Richardson WD, Kessaris N (2005) A subset of oligodendrocytes generated from radial glia in the dorsal spinal cord. Development 132:1951–1959

    CAS  PubMed  Google Scholar 

  • Foote AK, Blakemore WF (2005) Repopulation of oligodendrocyte progenitor cell depleted tissue in a model of chronic demyelination. Neuropathol Appl Neurobiol 31:105–114

    CAS  PubMed  Google Scholar 

  • Fortin D, Rom E, Sun H, Yayon A, Bansal R (2005) Distinct fibroblast growth factor (FGF)/FGF receptor signaling pairs initiate diverse cellular responses in the oligodendrocyte lineage. J Neurosci 25:7470–7479

    CAS  PubMed  Google Scholar 

  • Franklin RJ, Ffrench-Constant C (2008) Remyelination in the CNS: from biology to therapy. Nat Rev Neurosci 9:839–855

    CAS  PubMed  Google Scholar 

  • Franklin RJ, Kotter MR (2008) The biology of CNS remyelination: the key to therapeutic advances. J Neurol 255:19–25

    CAS  PubMed  Google Scholar 

  • Fröhlich N, Nagy B, Hovhannisyan A, Kukley M (2011) Fate of neuron-glia synapses during proliferation and differentiation of NG2 cells. J Anat 219:18–32

    PubMed  Google Scholar 

  • Frost EE, Nielsen JA, Le TQ, Armstrong RC (2003) PDGF and FGF2 regulate oligodendrocyte progenitor responses to demyelination. J Neurobiol 54:457–472

    CAS  PubMed  Google Scholar 

  • Frost EE, Zhou Z, Krasnesky K, Armstrong RC (2009) Initiation of oligodendrocyte progenitor cell migration by a PDGF-A activated extracellular regulated kinase (ERK) signaling pathway. Neurochem Res 34:169–181

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fruttiger M, Karlsson L, Hall AC, Abramsson A, Calver AR, Boström H, Willetts K, Bertold CH, Heath JK, Betsholtz C, Richardson WD (1999) Defective oligodendrocyte development and severe hypomyelination in PDGF-A knockout mice. Development 126:457–467

    CAS  PubMed  Google Scholar 

  • Furusho M, Kaga Y, Ishii A, Hébert JM, Bansal R (2011) Fibroblast growth factor signaling is required for the generation of oligodendrocyte progenitors from the embryonic forebrain. J Neurosci 31:5055–5066

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gallo V, Zhou JM, McBain CJ, Wright P, Knutson PL, Armstrong RC (1996) Oligodendrocyte progenitor cell proliferation and lineage progression are regulated by glutamate receptor-mediated K+ channel block. J Neurosci 16:2659–2670

    CAS  PubMed  Google Scholar 

  • Ge WP, Zhou W, Luo Q, Jan LY, Jan YN (2009) Dividing glial cells maintain differentiated properties including complex morphology and functional synapses. Proc Natl Acad Sci U S A 106:328–333

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ghiani CA, Yuan X, Eisen AM, Knutson PL, DePinho RA, McBain CJ, Gallo V (1999) Voltage-activated K+ channels and membrane depolarization regulate accumulation of the cyclin-dependent kinase inhibitors p27(Kip1) and p21(CIP1) in glial progenitor cells. J Neurosci 19:5380–5392

    CAS  PubMed  Google Scholar 

  • Goldman SA, Nedergaard M, Windrem MS (2012) Glial progenitor cell-based treatment and modeling of neurological disease. Science 338:491–495

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gonzalez-Perez O, Romero-Rodriguez R, Soriano-Navarro M, Garcia-Verdugo JM, Alvarez-Buylla A (2009) Epidermal growth factor induces the progeny of subventricular zone type B cells to migrate and differentiate into oligodendrocytes. Stem Cells 27:2032–2043

    CAS  PubMed Central  PubMed  Google Scholar 

  • Goretzki L, Burg MA, Grako KA, Stallcup WB (1999) High-affinity binding of basic fibroblast growth factor and platelet-derived growth factor-AA to the core protein of the NG2 proteoglycan. J Biol Chem 274:16831–16837

    CAS  PubMed  Google Scholar 

  • Gudz TI, Komuro H, Macklin WB (2006) Glutamate stimulates oligodendrocyte progenitor migration mediated via an alphav integrin/myelin proteolipid protein complex. J Neurosci 26:2458–2466

    CAS  PubMed  Google Scholar 

  • Guo F, Maeda Y, Ma J, Xu J, Horiuchi M, Miers L, Vaccarino F, Pleasure D (2010) Pyramidal neurons are generated from oligodendroglial progenitor cells in adult piriform cortex. J Neurosci 30:12036–12049

    CAS  PubMed Central  PubMed  Google Scholar 

  • He L, Lu QR (2013) Coordinated control of oligodendrocyte development by extrinsic and intrinsic signaling cues. Neurosci Bull 29:129–143

    CAS  PubMed  Google Scholar 

  • Hinks GL, Franklin RJ (2000) Delayed changes in growth factor gene expression during slow remyelination in the CNS of aged rats. Mol Cell Neurosci 16:542–556

    CAS  PubMed  Google Scholar 

  • Hinks GL, Chari DM, O’Leary MT, Zhao C, Keirstead HS, Blakemore WF, Franklin RJ (2001) Depletion of endogenous oligodendrocyte progenitors rather than increased availability of survival factors is a likely explanation for enhanced survival of transplanted oligodendrocyte progenitors in X-irradiated compared to normal CNS. Neuropathol Appl Neurobiol 27:59–67

    CAS  PubMed  Google Scholar 

  • Howng SYB, Avila RL, Emery B, Traka M, Lin W, Watkins T, Cook S, Bronson R, Davisson M, Barres BA, Popko B (2010) ZFP191 is required by oligodendrocytes for CNS myelination. Genes Dev 24:301–311

    CAS  PubMed  Google Scholar 

  • Huang JK, Jarjour AA, Nait Oumesmar B, Kerninon C, Williams A, Krezel W, Kagechika H, Bauer J, Zhao C, Baron-Van Evercooren A, Chambon P, Ffrench-Constant C, Franklin RJ (2011) Retinoid X receptor gamma signaling accelerates CNS remyelination. Nat Neurosci 14:45–53

    CAS  PubMed  Google Scholar 

  • Hughes EG, Kang SH, Fukaya M, Bergles DE (2013) Oligodendrocyte progenitors balance growth with self-repulsion to achieve homeostasis in the adult brain. Nat Neurosci 16:668–676

    CAS  PubMed  Google Scholar 

  • Inoue K, Osaka H, Imaizumi K, Nezu A, Takanashi J, Arii J, Murayama K, Ono J, Kikawa Y, Mito T, Shaffer LG, Lupski JR (1999) Proteolipid protein gene duplications causing Pelizaeus-Merzbacher disease: molecular mechanism and phenotypic manifestations. Ann Neurol 45:624–632

    CAS  PubMed  Google Scholar 

  • Irvine KA, Blakemore WF (2007) A different regional response by mouse oligodendrocyte progenitor cells (OPCs) to high-dose X-irradiation has consequences for repopulating OPC-depleted normal tissue. Eur J Neurosci 25:417–424

    PubMed  Google Scholar 

  • Ivkovic S, Canoll P, Goldman JE (2008) Constitutive EGFR signaling in oligodendrocyte progenitors leads to diffuse hyperplasia in postnatal white matter. J Neurosci 28:914–922

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jablonska B, Aguirre A, Raymond M, Szabo G, Kitabatake Y, Sailor KA, Ming GL, Song H, Gallo V (2010) Chordin-induced lineage plasticity of adult SVZ neuroblasts after demyelination. Nat Neurosci 13:541–550

    CAS  PubMed  Google Scholar 

  • Jaerve A, Müller HW (2012) Chemokines in CNS injury and repair. Cell Tissue Res 349:229–248

    CAS  PubMed  Google Scholar 

  • Jarjour AA, Manitt C, Moore SW, Thompson KM, Yuh SJ, Kennedy TE (2003) Netrin-1 is a chemorepellent for oligodendrocyte precursor cells in the embryonic spinal cord. J Neurosci 23:3735–3744

    CAS  PubMed  Google Scholar 

  • Jeffery ND, Blakemore WF (1997) Locomotor deficits induced by experimental spinal cord demyelination are abolished by spontaneous remyelination. Brain 120:27–37

    PubMed  Google Scholar 

  • Jessberger S, Toni N, Clemenson GD Jr, Ray J, Gage FH (2008) Directed differentiation of hippocampal stem/progenitor cells in the adult brain. Nat Neurosci 11:888–893

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kang SH, Fukaya M, Yang JK, Rothstein JD, Bergles DE (2010) NG2+ CNS glial progenitors remain committed to the oligodendrocyte lineage in postnatal life and following neurodegeneration. Neuron 68:668–681

    CAS  PubMed Central  PubMed  Google Scholar 

  • Keirstead HS, Blakemore WF (1999) The role of oligodendrocytes and oligodendrocyte progenitors in CNS remyelination. Adv Exp Med Biol 468:183–197

    CAS  PubMed  Google Scholar 

  • Kessaris N, Fogarty M, Iannarelli P, Grist M, Wegner M, Richardson WD (2006) Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage. Nat Neurosci 9:173–179

    CAS  PubMed  Google Scholar 

  • Knoblich JA (2010) Asymmetric cell division: recent developments and their implications for tumour biology. Nat Rev Mol Cell Biol 11:849–860

    CAS  PubMed  Google Scholar 

  • Knutson P, Ghiani CA, Zhou JM, Gallo V, McBain CJ (1997) K+ channel expression and cell proliferation are regulated by intracellular sodium and membrane depolarization in oligodendrocyte progenitor cells. J Neurosci 17:2669–2682

    CAS  PubMed  Google Scholar 

  • Koenning M, Jackson S, Hay CM, Faux C, Kilpatrick TJ, Willingham M, Emery B (2012) Myelin gene regulatory factor is required for maintenance of myelin and mature oligodendrocyte identity in the adult CNS. J Neurosci 32:12528–12542

    CAS  PubMed  Google Scholar 

  • Kondo T, Raff M (2000) Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells. Science 289:1754–1757

    CAS  PubMed  Google Scholar 

  • Kucharova K, Stallcup WB (2010) The NG2 proteoglycan promotes oligodendrocyte progenitor proliferation and developmental myelination. Neuroscience 166:185–194

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kukley M, Kiladze M, Tognatta R, Hans M, Swandulla D, Schramm J, Dietrich D (2008) Glial cells are born with synapses. FASEB J 22:2957–2969

    CAS  PubMed  Google Scholar 

  • Kukley M, Nishiyama A, Dietrich D (2010) The fate of synaptic input to NG2 glial cells: neurons specifically downregulate transmitter release onto differentiating oligodendroglial cells. J Neurosci 30:8320–8331

    CAS  PubMed  Google Scholar 

  • Lachapelle F, Gumpel M, Baulac C, Jacque C (1983) Transplantation of fragments of CNS into the brains of shiverer mutant mice: extensive myelination by transplanted oligodendrocytes. Dev Neurosci 6:326–334

    Google Scholar 

  • Li H, Richardson WD (2009) Genetics meets epigenetics: HDACs and Wnt signaling in myelin development and regeneration. Nat Neurosci 12:815–817

    CAS  PubMed  Google Scholar 

  • Li H, Lu Y, Smith HK, Richardson WD (2007) Olig1 and Sox10 interact synergistically to drive myelin basic protein transcription in oligodendrocytes. J Neurosci 27:14375–14382

    CAS  PubMed  Google Scholar 

  • Liebetanz D, Merkler D (2006) Effects of commissural de- and remyelination on motor skill behaviour in the cuprizone mouse model of multiple sclerosis. Exp Neurol 202:217–224

    CAS  PubMed  Google Scholar 

  • Lin SC, Bergles DE (2004) Synaptic signaling between GABAergic interneurons and oligodendrocyte precursor cells in the hippocampus. Nat Neurosci 7:24–32

    CAS  PubMed  Google Scholar 

  • Liu C, Sage JC, Miller MR, Verhaak RG, Hippenmeyer S, Vogel H, Foreman O, Bronson RT, Nishiyama A, Luo L, Zong H (2011) Mosaic analysis with double markers reveals tumor cell of origin in glioma. Cell 146:209–221

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lu QR, Yuk D, Alberta JA, Zhu Z, Pawlitzky I, Chan J, McMahon AP, Stiles CD, Rowitch DH (2000) Sonic hedgehog—regulated oligodendrocyte lineage genes encoding bHLH proteins in the mammalian central nervous system. Neuron 25:317–329

    CAS  PubMed  Google Scholar 

  • Ludwin SK, Maitland M (1984) Long-term remyelination fails to reconstitute normal thickness of central myelin sheaths. J Neurol Sci 64:193–198

    CAS  PubMed  Google Scholar 

  • Magnus T, Carmen J, Deleon J, Xue H, Pardo AC, Lepore AC, Mattson MP, Rao MS, Maragakis NJ (2008) Adult glial precursor proliferation in mutant SOD1G93A mice. Glia 56:200–208

    PubMed  Google Scholar 

  • Mangin JM, Gallo V (2011) The curious case of NG2 cells: transient trend or game changer? ASN Neuro 3:e00052

    PubMed Central  PubMed  Google Scholar 

  • Mangin JM, Li P, Scafidi J, Gallo V (2012) Experience-dependent regulation of NG2 progenitors in the developing barrel cortex. Nat Neurosci 15:1192–1194

    CAS  PubMed Central  PubMed  Google Scholar 

  • McKinnon RD, Matsui T, Dubois-Dalcq M, Aaronson SA (1990) FGF modulates the PDGF-driven pathway of oligodendrocyte development. Neuron 5:603–614

    CAS  PubMed  Google Scholar 

  • Menn B, Garcia-Verdugo JM, Yaschine C, Gonzalez-Perez O, Rowitch D, Alvarez-Buylla A (2006) Origin of oligodendrocytes in the subventricular zone of the adult brain. J Neurosci 26:7907–7918

    CAS  PubMed  Google Scholar 

  • Milner R, Anderson HJ, Rippon RF, McKay JS, Franklin RJ, Marchionni MA, Reynolds R, Ffrench-Constant C (1997) Contrasting effects of mitogenic growth factors on oligodendrocyte precursor cell migration. Glia 19:85–90

    CAS  PubMed  Google Scholar 

  • Mimault C, Giraud G, Courtois V, Cailloux F, Boire JY, Dastugue B, Boespflug-Tanguy O (1999) Proteolipoprotein gene analysis in 82 patients with sporadic Pelizaeus-Merzbacher disease: duplications, the major cause of the disease, originate more frequently in male germ cells, but point mutations do not. The Clinical European Network on brain dysmyelinating disease. Am J Hum Genet 65:360–369

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ming X, Chew LJ, Gallo V (2013) Transgenic overexpression of sox17 promotes oligodendrocyte development and attenuates demyelination. J Neurosci 33:12528–12542

    CAS  PubMed  Google Scholar 

  • Mirsky R, Woodhoo A, Parkinson DB, Arthur-Farraj P, Bhaskaran A, Jessen KR (2008) Novel signals controlling embryonic Schwann cell development, myelination and dedifferentiation. J Peripher Nerv Syst 13:122–135

    PubMed  Google Scholar 

  • Moll NM, Hong E, Fauveau M, Naruse M, Kerninon C, Tepavcevic V, Klopstein A, Seilhean D, Chew LJ, Gallo V, Oumesmar BN (2013) SOX17 is expressed in regenerating oligodendrocytes in experimental models of demyelination and in multiple sclerosis. Glia 61:1659–1672

    CAS  PubMed  Google Scholar 

  • Murtie JC, Zhou YX, Le TQ, Vana AC, Armstrong RC (2005) PDGF and FGF2 pathways regulate distinct oligodendrocyte lineage responses in experimental demyelination with spontaneous remyelination. Neurobiol Dis 19:171–182

    CAS  PubMed  Google Scholar 

  • Nait-Oumesmar B, Decker L, Lachapelle F, Avellana-Adalid V, Bachelin C, Van Evercooren AB (1999) Progenitor cells of the adult mouse subventricular zone proliferate, migrate and differentiate into oligodendrocytes after demyelination. Eur J Neurosci 11:4357–4366

    CAS  PubMed  Google Scholar 

  • Nishiyama A, Lin XH, Giese N, Heldin CH, Stallcup WB (1996) Co-localization of NG2 proteoglycan and PDGF alpha-receptor on O2A progenitor cells in the developing rat brain. J Neurosci Res 43:299–314

    CAS  PubMed  Google Scholar 

  • Ohya W, Funakoshi H, Kurosawa T, Nakamura T (2007) Hepatocyte growth factor (HGF) promotes oligodendrocyte progenitor cell proliferation and inhibits its differentiation during postnatal development in the rat. Brain Res 1147:51–65

    CAS  PubMed  Google Scholar 

  • Ono K, Yokota S, Tsumori T, Kishi T, Yasui Y (1999) Development of macroglial cells in the embryonic chick optic nerve. Brain Res Dev Brain Res 118:211–215

    CAS  PubMed  Google Scholar 

  • Orentas DM, Hayes JE, Dyer KL, Miller RH (1999) Sonic hedgehog signaling is required during the appearance of spinal cord oligodendrocyte precursors. Development 126:2419–2429

    CAS  PubMed  Google Scholar 

  • Patneau DK, Wright PW, Winters C, Mayer ML, Gallo V (1994) Glial cells of the oligodendrocyte lineage express both kainate- and AMPA-preferring subtypes of glutamate receptor. Neuron 12:357–371

    CAS  PubMed  Google Scholar 

  • Persson AI, Petritsch C, Swartling FJ, Itsara M, Sim FJ, Auvergne R, Goldenberg DD, Vandenberg SR, Nguyen KN, Yakovenko S, Ayers-Ringler J, Nishiyama A, Stallcup WB, Berger MS, Bergers G, McKnight TR, Goldman SA, Weiss WA (2010) Non-stem cell origin for oligodendroglioma. Cancer Cell 18:669–682

    CAS  PubMed Central  PubMed  Google Scholar 

  • Piaton G, Aigrot MS, Williams A, Moyon S, Tepavcevic V, Moutkine I, Gras J, Matho KS, Schmitt A, Soellner H, Huber AB, Ravassard P, Lubetzki C (2011) Class 3 semaphorins influence oligodendrocyte precursor recruitment and remyelination in adult central nervous system. Brain 134:1156–1167

    PubMed  Google Scholar 

  • Picard-Riera N, Decker L, Delarasse C, Goude K, Nait-Oumesmar B, Liblau R, Pham-Dinh D, Evercooren AB (2002) Experimental autoimmune encephalomyelitis mobilizes neural progenitors from the subventricular zone to undergo oligodendrogenesis in adult mice. Proc Natl Acad Sci U S A 99:13211–13216

    CAS  PubMed Central  PubMed  Google Scholar 

  • Psachoulia K, Jamen F, Young KM, Richardson WD (2009) Cell cycle dynamics of NG2 cells in the postnatal and ageing brain. Neuron Glia Biol 5:57–67

    PubMed  Google Scholar 

  • Ramírez-Castillejo C, Sánchez-Sánchez F, Andreu-Agulló C, Ferrón SR, Aroca-Aguilar JD, Sánchez P, Mira H, Escribano J, Fariñas I (2006) Pigment epithelium-derived factor is a niche signal for neural stem cell renewal. Nat Neurosci 9:331–339

    PubMed  Google Scholar 

  • Redwine JM, Armstrong RC (1998) In vivo proliferation of oligodendrocyte progenitors expressing PDGFαR during early remyelination. J Neurobiol 37:413–428

    CAS  PubMed  Google Scholar 

  • Reynolds R, Dawson M, Papadopoulos D, Polito A, Di Bello IC, Pham-Dinh D, Levine J (2002) The response of NG2-expressing oligodendrocyte progenitors to demyelination in MOG-EAE and MS. J Neurocytol 31:523–536

    PubMed  Google Scholar 

  • Richardson WD, Pringle N, Mosley MJ, Westermark B, Dubois-Dalcq M (1988) A role for platelet-derived growth factor in normal gliogenesis in the central nervous system. Cell 53:309–319

    CAS  PubMed  Google Scholar 

  • Richardson WD, Kessaris N, Pringle N (2006) Oligodendrocyte wars. Nat Rev Neurosci 7:11–18

    CAS  PubMed  Google Scholar 

  • Rivers LE, Young KM, Rizzi M, Jamen F, Psachoulia K, Wade A, Kessaris N, Richardson WD (2008) PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice. Nat Neurosci 11:1392–1401

    CAS  PubMed  Google Scholar 

  • Roach A, Takahashi N, Pravtcheva D, Ruddle F, Hood L (1985) Chromosomal mapping of mouse myelin basic protein gene and structure and transcription of the partially deleted gene in shiverer mutant mice. Cell 42:149–155

    CAS  PubMed  Google Scholar 

  • Robel S, Berninger B, Götz M (2011) The stem cell potential of glia: lessons from reactive gliosis. Nat Rev Neurosci 12:88–104

    CAS  PubMed  Google Scholar 

  • Robins SC, Villemain A, Liu X, Djogo T, Kryzskaya D, Storch KF, Kokoeva MV (2013) Extensive regenerative plasticity among adult NG2-glia populations is exclusively based on self-renewal. Glia 61:1735–1747

    PubMed  Google Scholar 

  • Rosenberg SS, Kelland EE, Tokar E, De la Torre AR, Chan JR (2008) The geometric and spatial constraints of the microenvironment induce oligodendrocyte differentiation. Proc Natl Acad Sci U S A 105:14662–14667

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rossi D, Brambilla L, Valori CF, Roncoroni C, Crugnola A, Yokota T, Bredesen DE, Volterra A (2008) Focal degeneration of astrocytes in amyotrophic lateral sclerosis. Cell Death Differ 15:1691–1700

    CAS  PubMed  Google Scholar 

  • Rowitch DH (2004) Glial specification in the vertebrate neural tube. Nat Rev Neurosci 5:409–419

    CAS  PubMed  Google Scholar 

  • Sellers DL, Maris DO, Horner PJ (2009) Postinjury niches induce temporal shifts in progenitor fates to direct lesion repair after spinal cord injury. J Neurosci 29:6722–6733

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shen S, Sandoval J, Swiss VA, Li J, Dupree J, Franklin RJ, Casaccia-Bonnefil P (2008) Age-dependent epigenetic control of differentiation inhibitors is critical for remyelination efficiency. Nat Neurosci 11:1024–1034

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shihabuddin LS, Horner PJ, Ray J, Gage FH (2000) Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus. J Neurosci 20:8727–8735

    CAS  PubMed  Google Scholar 

  • Small RK, Riddle P, Noble M (1987) Evidence for migration of oligodendrocyte—type-2 astrocyte progenitor cells into the developing rat optic nerve. Nature 328:55–57

    Google Scholar 

  • Smith KJ, Blakemore WF, McDonald WI (1979) Central remyelination restores secure conduction. Nature 280:395–396

    CAS  PubMed  Google Scholar 

  • Sohn J, Natale J, Chew LJ, Belachew S, Cheng Y, Aguirre A, Lytle J, Nait-Oumesmar B, Kerninon C, Kanai-Azuma M, Kanai Y, Gallo V (2006) Identification of Sox17 as a transcription factor that regulates oligodendrocyte development. J Neurosci 26:9722–9735

    CAS  PubMed  Google Scholar 

  • Sohn J, Selvaraj V, Wakayama K, Orosco L, Lee E, Crawford SE, Guo F, Lang J, Horiuchi M, Zarbalis K, Itoh T, Deng W, Pleasure D (2012) PEDF is a novel oligodendrogenic morphogen acting on the adult SVZ and corpus callosum. J Neurosci 32:12152–12164

    CAS  PubMed Central  PubMed  Google Scholar 

  • Spassky N et al (2002) Directional guidance of oligodendroglial migration by class 3 semaphorins and netrin-1. J Neurosci 22:5992–6004

    CAS  PubMed  Google Scholar 

  • Stallcup WB (1981) The NG2 antigen, a putative lineage marker: immunofluorescent localization in primary cultures of rat brain. Dev Biol 83:154–165

    CAS  PubMed  Google Scholar 

  • Steindler DA (1993) Glial boundaries in the developing nervous system. Annu Rev Neurosci 16:445–470

    CAS  PubMed  Google Scholar 

  • Stolt CC, Rehberg S, Ader M, Lommes P, Riethmacher D, Schachner M, Bartsch U, Wegner M (2002) Terminal differentiation of myelin-forming oligodendrocytes depends on the transcription factor Sox10. Genes Dev 16:165–170

    CAS  PubMed  Google Scholar 

  • Sugiarto S, Persson AI, Munoz EG, Waldhuber M, Lamagna C, Andor N, Hanecker P, Ayers-Ringler J, Phillips J, Siu J, Lim DA, Vandenberg S, Stallcup W, Berger MS, Bergers G, Weiss WA, Petritsch C (2011) Asymmetry-defective oligodendrocyte progenitors are glioma precursors. Cancer Cell 20:328–340

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sugimoto Y, Taniguchi M, Yagi T, Akagi Y, Nojyo Y, Tamamaki N (2001) Guidance of glial precursor cell migration by secreted cues in the developing optic nerve. Development 128:3321–3330

    CAS  PubMed  Google Scholar 

  • Tanaka Y, Tozuka Y, Takata T, Shimazu N, Matsumura N, Ohta A, Hisatsune T (2009) Excitatory GABAergic activation of cortical dividing glial cells. Cereb Cortex 19:2181–2195

    PubMed  Google Scholar 

  • Tatsumi K, Takebayashi H, Manabe T, Tanaka KF, Makinodan M, Yamauchi T, Makinodan E, Matsuyoshi H, Okuda H, Ikenaka K, Wanaka A (2008) Genetic fate mapping of Olig2 progenitors in the injured adult cerebral cortex reveals preferential differentiation into astrocytes. J Neurosci Res 86:3494–3502

    CAS  PubMed  Google Scholar 

  • Tekki-Kessaris N, Woodruff R, Hall AC, Gaffield W, Kimura S, Stiles CD, Rowitch DH, Richardson WD (2001) Hedgehog-dependent oligodendrocyte lineage specification in the telencephalon. Development 128:2545–2554

    CAS  PubMed  Google Scholar 

  • Touraine RL, Attié-Bitach T, Manceau E, Korsch E, Sarda P, Pingault V, Encha-Razavi F, Pelet A, Augé J, Nivelon-Chevallier A, Holschneider AM, Munnes M, Doerfler W, Goossens M, Munnich A, Vekemans M, Lyonnet S (2000) Neurological phenotype in Waardenburg syndrome type 4 correlates with novel SOX10 truncating mutations and expression in developing brain. Am J Hum Genet 66:1496–1503

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tripathi RB, Clarke LE, Burzomato V, Kessaris N, Anderson PN, Attwell D, Richardson WD (2011) Dorsally and ventrally derived oligodendrocytes have similar electrical properties but myelinate preferred tracts. J Neurosci 31:6809–6819

    CAS  PubMed  Google Scholar 

  • Tsai HH, Frost E, To V, Robinson S, Ffrench-Constant C, Geertman R, Ransohoff RM, Miller RH (2002) The chemokine receptor CXCR2 controls positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration. Cell 110:373–383

    CAS  PubMed  Google Scholar 

  • Vallstedt A, Klos JM, Ericson J (2005) Multiple dorsoventral origins of oligodendrocyte generation in the spinal cord and hindbrain. Neuron 45:55–67

    CAS  PubMed  Google Scholar 

  • Van Keuren ML, Gavrilina GB, Filipiak WE, Zeidler MG, Saunders TL (2009) Generating transgenic mice from bacterial artificial chromosomes: transgenesis efficiency, integration and expression outcomes. Transgenic Res 18:769–785

    CAS  PubMed Central  PubMed  Google Scholar 

  • Vautier F, Belachew S, Chittajallu R, Gallo V (2004) Shaker-type potassium channel subunits differentially control oligodendrocyte progenitor proliferation. Glia 48:337–345

    PubMed  Google Scholar 

  • Vélez-Fort M, Audinat E, Angulo MC (2009) Functional alpha 7-containing nicotinic receptors of NG2-expressing cells in the hippocampus. Glia 57:1104–1114

    PubMed  Google Scholar 

  • Vora P, Pillai PP, Zhu W, Mustapha J, Namaka MP, Frost EE (2011) Differential effects of growth factors on oligodendrocyte progenitor migration. Eur J Cell Biol 90:649–656

    CAS  PubMed  Google Scholar 

  • Vora P, Pillai P, Mustapha J, Kowal C, Shaffer S, Bose R, Namaka M, Frost EE (2012) CXCL1 regulation of oligodendrocyte progenitor cell migration is independent of calcium signaling. Exp Neurol 236:259–267

    CAS  PubMed  Google Scholar 

  • Wang S, Bates J, Li X, Schanz S, Chandler-Militello D, Levine C, Maherali N, Studer L, Hochedlinger K, Windrem M, Goldman SA (2013) Human iPSC-derived oligodendrocyte progenitor cells can myelinate and rescue a mouse model of congenital hypomyelination. Cell Stem Cell 12:252–264

    CAS  PubMed Central  PubMed  Google Scholar 

  • Watkins TA, Emery B, Mulinyawe S, Barres BA (2008) Distinct stages of myelination regulated by g-secretase and astrocytes in a rapidly myelinating CNS coculture system. Neuron 60:555–569

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wigmore P (2013) The effect of systemic chemotherapy on neurogenesis, plasticity and memory. Curr Top Behav Neurosci 15:211–240

    PubMed  Google Scholar 

  • Wolswijk G (1998) Oligodendrocyte regeneration in the adult rodent CNS and the failure of this process in multiple sclerosis. Prog Brain Res 117:233–247

    CAS  PubMed  Google Scholar 

  • Wolswijk G (2000) Oligodendrocyte survival, loss and birth in lesions of chronic-stage multiple sclerosis. Brain 123:105–115

    PubMed  Google Scholar 

  • Wolswijk G, Noble M (1989) Identification of an adult-specific glial progenitor cell. Development 105:387–400

    CAS  PubMed  Google Scholar 

  • Wolswijk G, Noble M (1992) Cooperation between PDGF and FGF converts slowly dividing O-2Aadult progenitor cells to rapidly dividing cells with characteristics of O-2Aperinatal progenitor cells. J Cell Biol 118:889–900

    CAS  PubMed  Google Scholar 

  • Woodruff RH, Fruttiger M, Richardson WD, Franklin RJ (2004) Platelet-derived growth factor regulates oligodendrocyte progenitor numbers in adult CNS and their response following CNS demyelination. Mol Cell Neurosci 25:252–262

    CAS  PubMed  Google Scholar 

  • Xin M, Yue T, Ma Z, Wu FF, Gow A, Lu QR (2005) Myelinogenesis and axonal recognition by oligodendrocytes in brain are uncoupled in Olig1-null mice. J Neurosci 25:1354–1365

    CAS  PubMed  Google Scholar 

  • Young KM, Psachoulia K, Tripathi RB, Dunn SJ, Cossell L, Attwell D, Tohyama K, Richardson WD (2013) Oligodendrocyte dynamics in the healthy adult CNS: evidence for myelin remodeling. Neuron 77:873–885

    CAS  PubMed  Google Scholar 

  • Yuan X, Eisen AM, McBain CJ, Gallo V (1998) A role for glutamate and its receptors in the regulation of oligodendrocyte development in cerebellar tissue slices. Development 125:2901–2914

    CAS  PubMed  Google Scholar 

  • Zhu X, Bergles DE, Nishiyama A (2008a) NG2 cells generate both oligodendrocytes and gray matter astrocytes. Development 135:145–157

    CAS  PubMed  Google Scholar 

  • Zhu X, Hill RA, Nishiyama A (2008b) NG2 cells generate oligodendrocytes and gray matter astrocytes in the spinal cord. Neuron Glia Biol 4:19–26

    PubMed  Google Scholar 

  • Zhu X, Hill RA, Dietrich D, Komitova M, Suzuki R, Nishiyama A (2011) Age-dependent fate and lineage restriction of single NG2 cells. Development 138:745–753

    CAS  PubMed  Google Scholar 

  • Zuchero JB, Barres BA (2013) Intrinsic and extrinsic control of oligodendrocyte development. Curr Opin Neurobiol 23:914. doi:10.1016/j.conb.2013.06.005, pii: S0959-4388(13)00124-4

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. French Institute of Health and Medical Research, U952, Pierre-and-Marie-Curie University, Paris, France

    Jean-Marie Mangin

Authors
  1. Jean-Marie Mangin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jean-Marie Mangin .

Editor information

Editors and Affiliations

  1. French Institute of Health and Medical Research U1130, French National Center for Scientific Research, Pierre-and-Marie-Curie University, Paris, France

    Marie-Pierre Junier

  2. Departments of Pediatrics and Pathology & Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York, USA

    Steven G. Kernie

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Mangin, JM. (2014). Regenerative Potential of NG2 Cells. In: Junier, MP., Kernie, S. (eds) Endogenous Stem Cell-Based Brain Remodeling in Mammals. Stem Cell Biology and Regenerative Medicine. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-7399-3_7

Download citation

Publish with us

Policies and ethics

Search

Navigation