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PMID: 19234458 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Forebrain ependymal cells are Notch-dependent and generate neuroblasts and astrocytes after stroke.

Nature neuroscience ·Vol. 12 ·No. 3 ·2009-03-00 ·Pages 259-67

Carlén M, Meletis K, Göritz C, Darsalia V, Evergren E, Tanigaki K, Amendola M, Barnabé-Heider F, Yeung MS, Naldini L, Honjo T, Kokaia Z, Shupliakov O, Cassidy RM, Lindvall O, Frisén J

Abstract

Neurons are continuously generated from stem cells in discrete regions in the adult mammalian brain. We found that ependymal cells lining the lateral ventricles were quiescent and did not contribute to adult neurogenesis under normal conditions in mice but instead gave rise to neuroblasts and astrocytes in response to stroke. Ependymal cell quiescence was actively maintained by canonical Notch signaling. Inhibition of this pathway in uninjured animals allowed ependymal cells to enter the cell cycle and produce olfactory bulb neurons, whereas forced Notch signaling was sufficient to block the ependymal cell response to stroke. Ependymal cells were depleted by stroke and failed to self-renew sufficiently to maintain their own population. Thus, although ependymal cells act as primary cells in the neural lineage to produce neurons and glial cells after stroke, they do not fulfill defining criteria for stem cells under these conditions and instead serve as a reservoir that is recruited by injury.

MeSH Terms
Animals Astrocytes/cytology,physiology Cell Differentiation/physiology Ependyma/cytology,physiology Growth Inhibitors/physiology Humans Mice Mice, Inbred ICR Mice, Transgenic Neurons/cytology,physiology Olfactory Bulb/cytology,physiology Phenotype Prosencephalon/cytology,physiology Receptor, Notch1/physiology Stem Cells/cytology,physiology Stroke/metabolism,pathology
Chemicals
Growth Inhibitors Receptor, Notch1
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Carlén Marie
Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, SE-171 77 Stockholm, Sweden.
Meletis Konstantinos
Göritz Christian
Darsalia Vladimer
Evergren Emma
Tanigaki Kenji
Amendola Mario
Barnabé-Heider Fanie
Yeung Maggie S Y
Naldini Luigi
Honjo Tasuku
Kokaia Zaal
Shupliakov Oleg
Cassidy Robert M
Lindvall Olle
Frisén Jonas
References (43)
43 references, click to expand
  1. The cell biology of neurogenesis.
    Nat Rev Mol Cell Biol. 2005 Oct;6(10):777-88 PMID: 16314867
  2. Functional identification of the actual and potential stem cell compartments in mouse spermatogenesis.
    Dev Cell. 2007 Feb;12(2):195-206 PMID: 17276338
  3. Forkhead transcription factor HFH-4 expression is temporally related to ciliogenesis.
    Am J Respir Cell Mol Biol. 1999 Aug;21(2):168-76 PMID: 10423398
  4. Reduced brain edema and infarction volume in mice lacking the neuronal isoform of nitric oxide synthase after transient MCA occlusion.
    J Cereb Blood Flow Metab. 1996 Jul;16(4):605-11 PMID: 8964799
  5. Progenitors resume generating neurons after temporary inhibition of neurogenesis by Notch activation in the mammalian cerebral cortex.
    Development. 2005 Mar;132(6):1295-304 PMID: 15750183
  6. Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis.
    Nat Med. 2005 Dec;11(12):1351-4 PMID: 16288281
  7. Notch signalling in vertebrate neural development.
    Nat Rev Neurosci. 2006 Feb;7(2):93-102 PMID: 16429119
  8. Notch-RBP-J signaling is involved in cell fate determination of marginal zone B cells.
    Nat Immunol. 2002 May;3(5):443-50 PMID: 11967543
  9. The winged helix transcription factor HFH-4 is expressed during choroid plexus epithelial development in the mouse embryo.
    Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3094-9 PMID: 9096351
  10. Phosphorylation of histone H3 is required for proper chromosome condensation and segregation.
    Cell. 1999 Apr 2;97(1):99-109 PMID: 10199406
  11. LeX/ssea-1 is expressed by adult mouse CNS stem cells, identifying them as nonependymal.
    Neuron. 2002 Aug 29;35(5):865-75 PMID: 12372282
  12. Adult neurogenesis and functional plasticity in neuronal circuits.
    Nat Rev Neurosci. 2006 Mar;7(3):179-93 PMID: 16495940
  13. SOX2, a persistent marker for multipotential neural stem cells derived from embryonic stem cells, the embryo or the adult.
    Dev Neurosci. 2004 Mar-Aug;26(2-4):148-65 PMID: 15711057
  14. Radial glia cells are candidate stem cells of ependymoma.
    Cancer Cell. 2005 Oct;8(4):323-35 PMID: 16226707
  15. Transfer of a foreign gene into the brain using adenovirus vectors.
    Nat Genet. 1993 Mar;3(3):224-8 PMID: 8485577
  16. Prominin, a novel microvilli-specific polytopic membrane protein of the apical surface of epithelial cells, is targeted to plasmalemmal protrusions of non-epithelial cells.
    Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12425-30 PMID: 9356465
  17. Radial glial identity is promoted by Notch1 signaling in the murine forebrain.
    Neuron. 2000 May;26(2):395-404 PMID: 10839358
  18. Control of the reversibility of cellular quiescence by the transcriptional repressor HES1.
    Science. 2008 Aug 22;321(5892):1095-100 PMID: 18719287
  19. Adult ependymal cells are postmitotic and are derived from radial glial cells during embryogenesis.
    J Neurosci. 2005 Jan 5;25(1):10-8 PMID: 15634762
  20. Long-term survival and cell death of newly generated neurons in the adult rat olfactory bulb.
    Eur J Neurosci. 2002 Nov;16(9):1681-9 PMID: 12431220
  21. Genetic manipulation of adult mouse neurogenic niches by in vivo electroporation.
    Nat Methods. 2008 Feb;5(2):189-96 PMID: 18204459
  22. Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain.
    J Neurosci. 1997 Jul 1;17(13):5046-61 PMID: 9185542
  23. RNA-binding protein Musashi family: roles for CNS stem cells and a subpopulation of ependymal cells revealed by targeted disruption and antisense ablation.
    Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):15194-9 PMID: 12407178
  24. Targeting expression of a transgene to the airway surface epithelium using a ciliated cell-specific promoter.
    Mol Ther. 2003 Oct;8(4):637-45 PMID: 14529837
  25. Robust in vivo gene transfer into adult mammalian neural stem cells by lentiviral vectors.
    Proc Natl Acad Sci U S A. 2004 Oct 12;101(41):14835-40 PMID: 15466696
  26. Direct in vivo gene transfer to ependymal cells in the central nervous system using recombinant adenovirus vectors.
    Nat Genet. 1993 Mar;3(3):229-34 PMID: 8485578
  27. Persistent expression of helix-loop-helix factor HES-1 prevents mammalian neural differentiation in the central nervous system.
    EMBO J. 1994 Apr 15;13(8):1799-805 PMID: 7909512
  28. From stem cell to progenitor and back again.
    Cell. 2007 Mar 9;128(5):825-6 PMID: 17350567
  29. Beta cells can be generated from endogenous progenitors in injured adult mouse pancreas.
    Cell. 2008 Jan 25;132(2):197-207 PMID: 18243096
  30. Identification of a neural stem cell in the adult mammalian central nervous system.
    Cell. 1999 Jan 8;96(1):25-34 PMID: 9989494
  31. Facultative endocrine progenitor cells in the adult pancreas.
    Cell. 2008 Jan 25;132(2):183-4 PMID: 18243094
  32. Notch signalling regulates stem cell numbers in vitro and in vivo.
    Nature. 2006 Aug 17;442(7104):823-6 PMID: 16799564
  33. Generalized lacZ expression with the ROSA26 Cre reporter strain.
    Nat Genet. 1999 Jan;21(1):70-1 PMID: 9916792
  34. Sox2 deficiency causes neurodegeneration and impaired neurogenesis in the adult mouse brain.
    Development. 2004 Aug;131(15):3805-19 PMID: 15240551
  35. Spinal cord injury reveals multilineage differentiation of ependymal cells.
    PLoS Biol. 2008 Jul 22;6(7):e182 PMID: 18651793
  36. Generation of functional radial glial cells by embryonic and adult forebrain neural stem cells.
    J Neurosci. 2003 Dec 17;23(37):11587-601 PMID: 14684861
  37. Neural stem cells confer unique pinwheel architecture to the ventricular surface in neurogenic regions of the adult brain.
    Cell Stem Cell. 2008 Sep 11;3(3):265-78 PMID: 18786414
  38. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain.
    Cell. 1999 Jun 11;97(6):703-16 PMID: 10380923
  39. Recombinant adenovirus: a gene transfer vector for study and treatment of CNS diseases.
    Exp Neurol. 1997 Mar;144(1):125-30 PMID: 9126161
  40. Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation.
    Nature. 2004 May 6;429(6987):41-6 PMID: 15129273
  41. Distinct stem cell populations regenerate the follicle and interfollicular epidermis.
    Dev Cell. 2005 Dec;9(6):855-61 PMID: 16326396
  42. Stroke induces ependymal cell transformation into radial glia in the subventricular zone of the adult rodent brain.
    J Cereb Blood Flow Metab. 2007 Jun;27(6):1201-12 PMID: 17200679
  43. CD133+ neural stem cells in the ependyma of mammalian postnatal forebrain.
    Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):1026-31 PMID: 18195354
Article Info
Journal
Nature neuroscience
Abbr.
Nat Neurosci
ISSN
1546-1726
DOI
10.1038/nn.2268
Published
2009-03-00
Epub
2009-00-22
Pages
259-67
Language
English
Region
United States
NLM ID
9809671
Subset
IM
Grants
Telethon · TGT06D02 · Italy
Corrections
CommentIn
PMID: 19238183
External Links
PubMed source DOI: 10.1038/nn.2268 View journal details
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