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The Journal of Neuroscience, June 1, 1999, 19(11):4462-4471
Adult Mammalian Forebrain Ependymal and Subependymal Cells
Demonstrate Proliferative Potential, but only Subependymal Cells Have
Neural Stem Cell Characteristics
Bernard J.
Chiasson,
Vincent
Tropepe,
Cindi M.
Morshead, and
Derek
van der Kooy
Neurobiology Research Group, Department of Anatomy and Cell
Biology, University of Toronto, Toronto, Canada, M5S 1A8
The adult derivatives of the embryonic forebrain germinal zones
consist of two morphologically distinct cell layers surrounding the
lateral ventricles: the ependyma and the subependyma. Cell cycle
analyses have revealed that at least two proliferating populations exist in this region, one that is constitutively proliferating and one
that is relatively quiescent and thought to include the endogenous
adult neural stem cells. Earlier studies demonstrated that specific
dissection of the region surrounding the lateral ventricles was
necessary for the in vitro isolation of multipotent, self-renewing neural stem cells. However, in these studies, the ependymal layer was not physically separated from the subependymal layer to identify the specific adult laminar localization of the neural
stem cells around the lateral ventricles. To determine which cellular
compartment in the adult forebrain contained the neural stem cells, we
isolated and cultured the ependyma separately from the subependyma and
tested for the presence of neural stem cells using the in
vitro neurosphere assay. We demonstrate that the ependymal
cells can proliferate in vitro to form sphere-like structures. However, the ependymal cells generating spheres do not have
the ability to self-renew (proliferate to form secondary spheres after
dissociation) nor to produce neurons, but rather only seem to generate
glial fibrillary acidic protein-positive ependymal cells when plated
under differentiation conditions in culture. On the other hand, a
subpopulation of subependymal cells do possess the self-renewing and
multipotential characteristics of neural stem cells. Therefore, the
adult forebrain neural stem cell resides within the subependymal compartment.
Key words:
ependyma; subependyma; neural stem cells; proliferation; adult; forebrain
Copyright © 1999 Society for Neuroscience 0270-6474/99/19114462-10$05.00/0
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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169 - 186.
[Abstract]
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|
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|

|
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|
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23(7):
2824 - 2832.
[Abstract]
[Full Text]
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|
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|

|
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|
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23(3):
895 - 906.
[Abstract]
[Full Text]
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|
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|

|
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|
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99(22):
14506 - 14511.
[Abstract]
[Full Text]
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|
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|

|
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|
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3594 - 3607.
[Abstract]
[Full Text]
[PDF]
|
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|

|
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|
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[Abstract]
[Full Text]
[PDF]
|
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|

|
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|
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87(2):
1076 - 1085.
[Abstract]
[Full Text]
[PDF]
|
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|

|
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|
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22(2):
437 - 445.
[Abstract]
[Full Text]
[PDF]
|
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|

|
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|
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21(18):
7153 - 7160.
[Abstract]
[Full Text]
[PDF]
|
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|

|
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|
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21(17):
6706 - 6717.
[Abstract]
[Full Text]
[PDF]
|
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|

|
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|
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J. Neurosci.,
August 15, 2001;
21(16):
6195 - 6205.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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February 1, 2001;
142(2):
812 - 822.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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97(26):
14720 - 14725.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
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Identification of a multipotent astrocytic stem cell in the immature and adult mouse brain
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November 22, 2000;
(2000)
250471697.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
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March 15, 2000;
20(6):
2218 - 2228.
[Abstract]
[Full Text]
[PDF]
|
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|
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|
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February 25, 2000;
287(5457):
1433 - 1438.
[Abstract]
[Full Text]
|
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|
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|
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276(32):
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[Full Text]
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|
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|
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|
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97(25):
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|
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|