Home LiteratureArticle Details
PMID: 19458241 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Postinjury niches induce temporal shifts in progenitor fates to direct lesion repair after spinal cord injury.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 29 ·No. 20 ·2009-05-20 ·Pages 6722-33

Sellers DL, Maris DO, Horner PJ

Abstract

Progenitors that express NG2-proteoglycan are the predominant self-renewing cells within the CNS. NG2 progenitors replenish oligodendrocyte populations within the intact stem cell niche, and cycling NG2 cells are among the first cells to react to CNS insults. We investigated the role of NG2 progenitors after spinal cord injury and how bone morphogen protein signals remodel the progressive postinjury (PI) niche. Progeny labeled by an NG2-specific reporter virus undergo a coordinated shift in differentiation profile. NG2 progeny born 24 h PI produce scar-forming astrocytes and transient populations of novel phagocytic astrocytes shown to contain denatured myelin within cathepsin-D-labeled endosomes, but NG2 progenitors born 7 d PI differentiate into oligodendrocytes and express myelin on processes that wrap axons. Analysis of spinal cord mRNA shows a temporal shift in the niche transcriptome of ligands that affect PI remodeling and direct progenitor differentiation. We conclude that NG2 progeny are diverse lineages that obey progressive cues after trauma to replenish the injured niche.

MeSH Terms
Analysis of Variance Animals Animals, Newborn Antigens/genetics,metabolism Apoptosis/genetics,physiology Caspase 3/metabolism Cell Differentiation/physiology Disease Models, Animal Glial Fibrillary Acidic Protein/metabolism Green Fluorescent Proteins/genetics Mice Myelin Basic Protein/metabolism Nerve Growth Factors/metabolism Proteoglycans/genetics,metabolism S100 Calcium Binding Protein beta Subunit S100 Proteins/metabolism Signal Transduction Spinal Cord Injuries/physiopathology,surgery Stem Cell Niche/pathology,physiopathology Stem Cell Transplantation/methods Stem Cells/metabolism,physiology Time Factors Transfection
Chemicals
Antigens Glial Fibrillary Acidic Protein Myelin Basic Protein Nerve Growth Factors Proteoglycans S100 Calcium Binding Protein beta Subunit S100 Proteins chondroitin sulfate proteoglycan 4 Green Fluorescent Proteins Caspase 3
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sellers Drew L
Department of Neurological Surgery, University of Washington, Seattle, Washington 98104, USA. drewfus@u.washington.edu
Maris Don O
Horner Philip J
References (68)
68 references, click to expand
  1. Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus.
    J Neurosci. 2000 Dec 1;20(23):8727-35 PMID: 11102479
  2. BMP and FGF regulate the development of EGF-responsive neural progenitor cells.
    Development. 2000 Nov;127(22):4993-5005 PMID: 11044412
  3. Signaling in adult neurogenesis: from stem cell niche to neuronal networks.
    Curr Opin Neurobiol. 2007 Jun;17(3):338-44 PMID: 17475475
  4. Amino acid sequence of human myelin basic protein peptide 45-89 as determined by mass spectrometry.
    J Biol Chem. 1984 Apr 25;259(8):5028-31 PMID: 6201481
  5. Neural stem cells from adult hippocampus develop essential properties of functional CNS neurons.
    Nat Neurosci. 2002 May;5(5):438-45 PMID: 11953752
  6. Pigment epithelium-derived factor is a niche signal for neural stem cell renewal.
    Nat Neurosci. 2006 Mar;9(3):331-9 PMID: 16491078
  7. BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3.
    Cell. 2003 Oct 31;115(3):281-92 PMID: 14636556
  8. Adult neurogenesis and the vascular Nietzsche.
    Neuron. 2002 Jun 13;34(6):856-8 PMID: 12086632
  9. Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons.
    J Cell Biol. 2003 Apr 14;161(1):169-86 PMID: 12682089
  10. CNTF induces GFAP in a S-100 alpha brain cell population: the pattern of CNTF-alpha R suggests an indirect mode of action.
    Brain Res Dev Brain Res. 1997 Feb 20;98(2):221-33 PMID: 9051264
  11. NG2 proteoglycan-expressing cells of the adult rat brain: possible involvement in the formation of glial scar astrocytes following stab wound.
    Glia. 2005 Feb;49(3):318-38 PMID: 15494983
  12. Lineage analysis using retroviral vectors.
    Methods. 1998 Apr;14(4):393-406 PMID: 9608510
  13. Microglial response to brain injury: a brief synopsis.
    Toxicol Pathol. 2000 Jan-Feb;28(1):28-30 PMID: 10668987
  14. Visualization of S100B-positive neurons and glia in the central nervous system of EGFP transgenic mice.
    J Comp Neurol. 2003 Mar 17;457(4):404-19 PMID: 12561079
  15. The glial scar and central nervous system repair.
    Brain Res Bull. 1999 Aug;49(6):377-91 PMID: 10483914
  16. Socializing with the neighbors: stem cells and their niche.
    Cell. 2004 Mar 19;116(6):769-78 PMID: 15035980
  17. Fate of endogenous stem/progenitor cells following spinal cord injury.
    J Comp Neurol. 2006 Oct 1;498(4):525-38 PMID: 16874803
  18. Increase of NG2-positive cells associated with radial glia following traumatic spinal cord injury in adult rats.
    J Neurocytol. 2005 Dec;34(6):459-69 PMID: 16902766
  19. Astroglia induce neurogenesis from adult neural stem cells.
    Nature. 2002 May 2;417(6884):39-44 PMID: 11986659
  20. Multipotent CNS stem cells are present in the adult mammalian spinal cord and ventricular neuroaxis.
    J Neurosci. 1996 Dec 1;16(23):7599-609 PMID: 8922416
  21. The role of oligodendrocytes and oligodendrocyte progenitors in CNS remyelination.
    Adv Exp Med Biol. 1999;468:183-97 PMID: 10635029
  22. Immunohistochemical co-localization of S-100b and the glial fibrillary acidic protein in rat brain.
    Neuroscience. 1986 Mar;17(3):857-65 PMID: 2422599
  23. A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function.
    J Neurosci. 2008 Jan 2;28(1):264-78 PMID: 18171944
  24. Glial cell loss, proliferation and replacement in the contused murine spinal cord.
    Eur J Neurosci. 2007 Mar;25(6):1711-24 PMID: 17432960
  25. The NG2 chondroitin sulfate proteoglycan: a multifunctional proteoglycan associated with immature cells.
    Perspect Dev Neurobiol. 1996;3(4):245-59 PMID: 9117258
  26. Noggin antagonizes BMP signaling to create a niche for adult neurogenesis.
    Neuron. 2000 Dec;28(3):713-26 PMID: 11163261
  27. Response of the oligodendrocyte progenitor cell population (defined by NG2 labelling) to demyelination of the adult spinal cord.
    Glia. 1998 Feb;22(2):161-70 PMID: 9537836
  28. NG2-expressing glial progenitor cells: an abundant and widespread population of cycling cells in the adult rat CNS.
    Mol Cell Neurosci. 2003 Oct;24(2):476-88 PMID: 14572468
  29. Astrocytic functions and physiological reactions to injury: the potential to induce and/or exacerbate neuronal dysfunction--a forum position paper.
    Neurotoxicology. 1998 Feb;19(1):7-17; discussion 37-8 PMID: 9498214
  30. Defining the NG2-expressing cell of the adult CNS.
    J Neurocytol. 2002 Jul-Aug;31(6-7):469-80 PMID: 14501217
  31. NG2 cells generate both oligodendrocytes and gray matter astrocytes.
    Development. 2008 Jan;135(1):145-57 PMID: 18045844
  32. The glial scar: its bearing on axonal elongation and transplantation approaches to CNS repair.
    Adv Neurol. 1988;47:87-138 PMID: 3278533
  33. Regeneration beyond the glial scar.
    Nat Rev Neurosci. 2004 Feb;5(2):146-56 PMID: 14735117
  34. Tumor necrosis factor-alpha regulation of the Id gene family in astrocytes and microglia during CNS inflammatory injury.
    Glia. 1999 Apr;26(2):139-52 PMID: 10384879
  35. Origin of the glial processes responsible for the spontaneous postnatal phagocytosis of boutons on cat spinal motoneurons.
    Cell Tissue Res. 1978 May 29;189(2):203-17 PMID: 657238
  36. Fate alteration of neuroepithelial cells from neurogenesis to astrocytogenesis by bone morphogenetic proteins.
    Neurosci Res. 2001 Dec;41(4):391-6 PMID: 11755226
  37. Glial influences on neural stem cell development: cellular niches for adult neurogenesis.
    Curr Opin Neurobiol. 2005 Oct;15(5):514-20 PMID: 16144763
  38. Myelin basic protein speciation.
    Prog Clin Biol Res. 1984;146:511-21 PMID: 6201921
  39. Behavioral and histological outcomes following graded spinal cord contusion injury in the C57Bl/6 mouse.
    Exp Neurol. 2001 Jun;169(2):239-54 PMID: 11358439
  40. Cell proliferation and nestin expression in the ependyma of the adult rat spinal cord after injury.
    J Neuropathol Exp Neurol. 1999 May;58(5):489-98 PMID: 10331437
  41. Interactions between ID and OLIG proteins mediate the inhibitory effects of BMP4 on oligodendroglial differentiation.
    Development. 2004 Sep;131(17):4131-42 PMID: 15280210
  42. The responses of oligodendrocyte precursor cells, astrocytes and microglia to a cortical stab injury, in the brain.
    Neuroscience. 2004;127(4):813-20 PMID: 15312894
  43. Origin and progeny of reactive gliosis: A source of multipotent cells in the injured brain.
    Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3581-6 PMID: 18299565
  44. NG2-expressing cells as oligodendrocyte progenitors in the normal and demyelinated adult central nervous system.
    J Anat. 2005 Dec;207(6):707-16 PMID: 16367798
  45. Functional significance of adult neurogenesis.
    Curr Opin Neurobiol. 2004 Apr;14(2):186-91 PMID: 15082323
  46. Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells.
    Science. 2004 May 28;304(5675):1338-40 PMID: 15060285
  47. Microglia in health and disease.
    J Neurosci Res. 2005 Aug 1;81(3):302-13 PMID: 15954124
  48. Identification of a neural stem cell in the adult mammalian central nervous system.
    Cell. 1999 Jan 8;96(1):25-34 PMID: 9989494
  49. A potential role for bone morphogenetic protein signalling in glial cell fate determination following adult central nervous system injury in vivo.
    Eur J Neurosci. 2007 Dec;26(11):3024-35 PMID: 18028109
  50. Bone marrow chimeric rats reveal the unique distribution of resident and recruited macrophages in the contused rat spinal cord.
    J Neuropathol Exp Neurol. 2001 Jul;60(7):676-85 PMID: 11444796
  51. A functional role for EGFR signaling in myelination and remyelination.
    Nat Neurosci. 2007 Aug;10(8):990-1002 PMID: 17618276
  52. Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury.
    Exp Neurol. 2008 Feb;209(2):378-88 PMID: 17662717
  53. Proliferation and differentiation of progenitor cells throughout the intact adult rat spinal cord.
    J Neurosci. 2000 Mar 15;20(6):2218-28 PMID: 10704497
  54. Activation and proliferation of endogenous oligodendrocyte precursor cells during ethidium bromide-induced demyelination.
    Exp Neurol. 1999 Dec;160(2):333-47 PMID: 10619551
  55. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.
    Development. 1993 Jun;118(2):401-15 PMID: 8223268
  56. A secreted glycoprotein induced by estrogen in human breast cancer cell lines.
    Cell. 1980 Jun;20(2):353-62 PMID: 7388945
  57. Spinal cord injury reveals multilineage differentiation of ependymal cells.
    PLoS Biol. 2008 Jul 22;6(7):e182 PMID: 18651793
  58. Cellular niches for endogenous neural stem cells in the adult brain.
    CNS Neurol Disord Drug Targets. 2007 Oct;6(5):336-41 PMID: 18045162
  59. Changing role of forebrain astrocytes during development, regenerative failure, and induced regeneration upon transplantation.
    J Comp Neurol. 1986 Sep 1;251(1):23-43 PMID: 3760257
  60. Construction and characterization of a highly complex retroviral library for lineage analysis.
    Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5704-8 PMID: 7777573
  61. bHLH transcription factor Olig1 is required to repair demyelinated lesions in the CNS.
    Science. 2004 Dec 17;306(5704):2111-5 PMID: 15604411
  62. Cell proliferation and replacement following contusive spinal cord injury.
    Glia. 2005 May;50(3):247-57 PMID: 15739189
  63. Proliferation of NG2-positive cells and altered oligodendrocyte numbers in the contused rat spinal cord.
    J Neurosci. 2001 May 15;21(10):3392-400 PMID: 11331369
  64. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain.
    Cell. 1999 Jun 11;97(6):703-16 PMID: 10380923
  65. For the long run: maintaining germinal niches in the adult brain.
    Neuron. 2004 Mar 4;41(5):683-6 PMID: 15003168
  66. Dynamic changes in the response of cells to positive hedgehog signaling during mouse limb patterning.
    Cell. 2004 Aug 20;118(4):505-16 PMID: 15315762
  67. A PCR primer bank for quantitative gene expression analysis.
    Nucleic Acids Res. 2003 Dec 15;31(24):e154 PMID: 14654707
  68. GFAP and astrogliosis.
    Brain Pathol. 1994 Jul;4(3):229-37 PMID: 7952264
Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.4538-08.2009
Email
drewfus@u.washington.edu
Published
2009-05-20
Pages
6722-33
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC2706133
Subset
IM
Grants
NINDS NIH HHS · R01 NS046724 · United States
NINDS NIH HHS · R01 NS046724-03 · United States
PHS HHS · NSO46724 · United States
External Links
PubMed source DOI: 10.1523/JNEUROSCI.4538-08.2009 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2