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Negative Regulation of Neural Stem/Progenitor Cell Proliferation by the Pten Tumor Suppressor Gene in Vivo
Matthias Groszer,124Rebecca Erickson,2Deirdre D. Scripture-Adams,5Ralf Lesche,12*Andreas Trumpp,7Jerome A. Zack,56Harley I. Kornblum,23Xin Liu,24Hong Wu12
The mechanisms controlling neural stem cell proliferation are
poorly understood. Here we demonstrate that the PTEN tumor suppressorplays an important role in regulating neural stem/progenitor cellsin
vivo and in vitro. Mice lacking PTEN exhibited enlarged,
histoarchitecturallyabnormal brains, which resulted from increased
cell proliferation,decreased cell death, and enlarged cell size.
Neurosphere culturesrevealed a greater proliferation capacity for
tripotent Pten-/- central nervous system
stem/progenitor cells, which can be attributed,at least in part, to a
shortened cell cycle. However, cell fatecommitments of the progenitors
were largely undisturbed. Our resultssuggest that PTEN negatively
regulates neural stem cell proliferation.
1 Howard Hughes Medical Institute,
2 Department of Molecular and Medical Pharmacology,
3 Department of Pediatrics,
4 Department of Pathology and Laboratory Medicine,
5 Department of Medicine and AIDS Institute,
6 Department of Microbiology and Molecular Genetics,
UCLA School of Medicine, Los Angeles, CA 90095, USA.
7 Institut Suisse de Recherche Expérimentale
sur le Cancer, Ch. de Boveresses 155, 1066 Epalinges/Lausanne,
Switzerland.
*
Present address: Epigenomics AG, Kastanienallee 24, 10435 Berlin, Germany.
To whom correspondence should be addressed. E-mail:
xliu{at}mednet.ucla.edu, hwu{at}mednet.ucla.edu
The editors suggest the following Related Resources on Science sites:
In Science Magazine
PERSPECTIVES
Josef M. Penninger and James Woodgett (7 December 2001) Science294 (5549), 2116.
[DOI: 10.1126/science.1067931] |Summary »|Full Text »|PDF »
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