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PMID: 18587391 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Directed differentiation of hippocampal stem/progenitor cells in the adult brain.

Nature neuroscience ·Vol. 11 ·No. 8 ·2008-08-00 ·Pages 888-93

Jessberger S, Toni N, Clemenson GD, Ray J, Gage FH

Abstract

Adult neurogenesis is a lifelong feature of brain plasticity; however, the potency of adult neural stem/progenitor cells in vivo remains unclear. We found that retrovirus-mediated overexpression of a single gene, the bHLH transcription factor Ascl1, redirected the fate of the proliferating adult hippocampal stem/progenitor (AHP) progeny and lead to the exclusive generation of cells of the oligodendrocytic lineage at the expense of newborn neurons, demonstrating that AHPs in the adult mouse brain are not irrevocably specified in vivo. These data indicate that AHPs have substantial plasticity, which might have important implications for the potential use of endogenous AHPs in neurological disease.

MeSH Terms
Animals Antigens, Differentiation/biosynthesis Basic Helix-Loop-Helix Transcription Factors/genetics,physiology Brain/cytology Cell Differentiation/genetics,physiology Cell Lineage Cell Survival/genetics Cells, Cultured Dentate Gyrus/cytology Female Gene Transfer Techniques Genes, Reporter Green Fluorescent Proteins/biosynthesis,genetics Hippocampus/cytology Homeodomain Proteins/biosynthesis,genetics Lateral Ventricles/cytology Mice Mice, Inbred C57BL Moloney murine leukemia virus/genetics Neurons/cytology,metabolism,virology Oligodendroglia/cytology,metabolism,virology Rats Species Specificity Stem Cells/cytology,physiology,virology Transcription Factors/biosynthesis,genetics
Chemicals
Antigens, Differentiation Ascl1 protein, mouse Basic Helix-Loop-Helix Transcription Factors Distal-less homeobox proteins Homeodomain Proteins Transcription Factors Green Fluorescent Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Jessberger Sebastian
Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, California 92037, USA. [email protected]
Toni Nicolas
Clemenson Gregory D
Ray Jasodhara
Gage Fred H
References (46)
46 references, click to expand
  1. In vivo analysis of Ascl1 defined progenitors reveals distinct developmental dynamics during adult neurogenesis and gliogenesis.
    J Neurosci. 2007 Nov 21;27(47):12764-74 PMID: 18032648
  2. Defining a molecular atlas of the hippocampus using DNA microarrays and high-throughput in situ hybridization.
    J Neurosci. 2004 Apr 14;24(15):3879-89 PMID: 15084669
  3. Loss of BETA2/NeuroD leads to malformation of the dentate gyrus and epilepsy.
    Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):865-70 PMID: 10639171
  4. Mash1 specifies neurons and oligodendrocytes in the postnatal brain.
    EMBO J. 2004 Nov 10;23(22):4495-505 PMID: 15496983
  5. Adult hippocampal neurogenesis in depression.
    Nat Neurosci. 2007 Sep;10(9):1110-5 PMID: 17726477
  6. A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain.
    Neuron. 2007 May 24;54(4):559-66 PMID: 17521569
  7. Neuronal fate determinants of adult olfactory bulb neurogenesis.
    Nat Neurosci. 2005 Jul;8(7):865-72 PMID: 15951811
  8. Neurons derived from radial glial cells establish radial units in neocortex.
    Nature. 2001 Feb 8;409(6821):714-20 PMID: 11217860
  9. In vivo analysis of quiescent adult neural stem cells responding to Sonic hedgehog.
    Nature. 2005 Oct 6;437(7060):894-7 PMID: 16208373
  10. Kainic acid induced seizures: neurochemical and histopathological changes.
    Neuroscience. 1983 Dec;10(4):1301-15 PMID: 6141539
  11. Ascl1 defines sequentially generated lineage-restricted neuronal and oligodendrocyte precursor cells in the spinal cord.
    Development. 2007 Jan;134(2):285-93 PMID: 17166924
  12. Becoming a new neuron in the adult olfactory bulb.
    Nat Neurosci. 2003 May;6(5):507-18 PMID: 12704391
  13. Combinatorial actions of patterning and HLH transcription factors in the spatiotemporal control of neurogenesis and gliogenesis in the developing spinal cord.
    Development. 2007 Apr;134(8):1617-29 PMID: 17344230
  14. FGF-2-responsive neuronal progenitors reside in proliferative and quiescent regions of the adult rodent brain.
    Mol Cell Neurosci. 1995 Oct;6(5):474-86 PMID: 8581317
  15. Differential properties of adult rat and mouse brain-derived neural stem/progenitor cells.
    Mol Cell Neurosci. 2006 Mar;31(3):560-73 PMID: 16426857
  16. Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection.
    Cell. 2002 Apr 5;109(1):75-86 PMID: 11955448
  17. NeuroD is required for differentiation of the granule cells in the cerebellum and hippocampus.
    Genes Dev. 1999 Jul 1;13(13):1647-52 PMID: 10398678
  18. The proneural determinant MASH1 regulates forebrain Dlx1/2 expression through the I12b intergenic enhancer.
    Development. 2007 May;134(9):1755-65 PMID: 17409112
  19. 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
  20. PDGFR alpha-positive B cells are neural stem cells in the adult SVZ that form glioma-like growths in response to increased PDGF signaling.
    Neuron. 2006 Jul 20;51(2):187-99 PMID: 16846854
  21. Deregulation of dorsoventral patterning by FGF confers trilineage differentiation capacity on CNS stem cells in vitro.
    Neuron. 2003 Oct 30;40(3):485-99 PMID: 14642274
  22. The adult mouse hippocampal progenitor is neurogenic but not a stem cell.
    J Neurosci. 2005 Nov 23;25(47):10815-21 PMID: 16306394
  23. Mechanisms of axon ensheathment and myelin growth.
    Nat Rev Neurosci. 2005 Sep;6(9):683-90 PMID: 16136172
  24. Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain.
    Cell. 2007 Sep 21;130(6):1146-58 PMID: 17825401
  25. In vivo fate analysis reveals the multipotent and self-renewal capacities of Sox2+ neural stem cells in the adult hippocampus.
    Cell Stem Cell. 2007 Nov;1(5):515-28 PMID: 18371391
  26. Functional neurogenesis in the adult hippocampus.
    Nature. 2002 Feb 28;415(6875):1030-4 PMID: 11875571
  27. Neurogenin 2 has an essential role in development of the dentate gyrus.
    Development. 2008 Jun;135(11):2031-41 PMID: 18448566
  28. Mammalian neural stem cells.
    Science. 2000 Feb 25;287(5457):1433-8 PMID: 10688783
  29. Dlx1 and Dlx2 control neuronal versus oligodendroglial cell fate acquisition in the developing forebrain.
    Neuron. 2007 Aug 2;55(3):417-33 PMID: 17678855
  30. Enriched monolayer precursor cell cultures from micro-dissected adult mouse dentate gyrus yield functional granule cell-like neurons.
    PLoS One. 2007 Apr 25;2(4):e388 PMID: 17460755
  31. The proneural gene Mash1 specifies an early population of telencephalic oligodendrocytes.
    J Neurosci. 2007 Apr 18;27(16):4233-42 PMID: 17442807
  32. Doublecortin expression levels in adult brain reflect neurogenesis.
    Eur J Neurosci. 2005 Jan;21(1):1-14 PMID: 15654838
  33. Mechanisms and functional implications of adult neurogenesis.
    Cell. 2008 Feb 22;132(4):645-60 PMID: 18295581
  34. Glutamate excitotoxicity in a model of multiple sclerosis.
    Nat Med. 2000 Jan;6(1):67-70 PMID: 10613826
  35. Wnt signalling regulates adult hippocampal neurogenesis.
    Nature. 2005 Oct 27;437(7063):1370-5 PMID: 16251967
  36. Ascl1 is required for oligodendrocyte development in the spinal cord.
    Development. 2008 Apr;135(7):1271-81 PMID: 18287202
  37. Multipotent cell lineages in early mouse development depend on SOX2 function.
    Genes Dev. 2003 Jan 1;17(1):126-40 PMID: 12514105
  38. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain.
    Cell. 1999 Jun 11;97(6):703-16 PMID: 10380923
  39. Mosaic organization of neural stem cells in the adult brain.
    Science. 2007 Jul 20;317(5836):381-4 PMID: 17615304
  40. For the long run: maintaining germinal niches in the adult brain.
    Neuron. 2004 Mar 4;41(5):683-6 PMID: 15003168
  41. Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus.
    J Neurosci. 2006 Jan 4;26(1):3-11 PMID: 16399667
  42. Selective vulnerability of late oligodendrocyte progenitors to hypoxia-ischemia.
    J Neurosci. 2002 Jan 15;22(2):455-63 PMID: 11784790
  43. Adult rodent neurogenic regions: the ventricular subependyma contains neural stem cells, but the dentate gyrus contains restricted progenitors.
    J Neurosci. 2002 Mar 1;22(5):1784-93 PMID: 11880507
  44. Glial specification in the vertebrate neural tube.
    Nat Rev Neurosci. 2004 May;5(5):409-19 PMID: 15100723
  45. Basic helix-loop-helix proteins and the timing of oligodendrocyte differentiation.
    Development. 2000 Jul;127(14):2989-98 PMID: 10862737
  46. IGF-I instructs multipotent adult neural progenitor cells to become oligodendrocytes.
    J Cell Biol. 2004 Jan 5;164(1):111-22 PMID: 14709544
Article Info
Journal
Nature neuroscience
Abbr.
Nat Neurosci
ISSN
1546-1726
DOI
10.1038/nn.2148
Email
[email protected]
Published
2008-08-00
Epub
2008-00-29
Pages
888-93
Language
English
Region
United States
NLM ID
9809671
PMCID
PMC2795354
Subset
IM
Grants
NINDS NIH HHS · R01 NS050217-03 · United States
NINDS NIH HHS · R01 NS052842-03 · United States
NINDS NIH HHS · R01 NS050217-04 · United States
NINDS NIH HHS · R01 NS050217 · United States
NINDS NIH HHS · R01 NS052842 · United States
External Links
PubMed source DOI: 10.1038/nn.2148 PMC Full Text View journal details
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