Negative regulation of neural stem/progenitor cell proliferation by the Pten tumor suppressor gene in vivo.
The mechanisms controlling neural stem cell proliferation are poorly understood. Here we demonstrate that the PTEN tumor suppressor plays an important role in regulating neural stem/progenitor cells in vivo and in vitro. Mice lacking PTEN exhibited enlarged, histoarchitecturally abnormal brains, which resulted from increased cell proliferation, decreased cell death, and enlarged cell size. Neurosphere cultures revealed 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 fate commitments of the progenitors were largely undisturbed. Our results suggest that PTEN negatively regulates neural stem cell proliferation.
Groszer
M
M
Howard Hughes Medical Institute, Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA 90095, USA.
Erickson
R
R
Scripture-Adams
D D
DD
Lesche
R
R
Trumpp
A
A
Zack
J A
JA
Kornblum
H I
HI
Liu
X
X
Wu
H
H
D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000166:cytology; D001921:Brain / Q000002:abnormalities / Q000166:cytology* / Q000196:embryology; D002452:Cell Count; D002454:Cell Differentiation; D002455:Cell Division; D019070:Cell Lineage; D048429:Cell Size; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D005452:Fluoresceins / Q000378:metabolism; D017353:Gene Deletion; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D064231:Nestin; D009474:Neurons / Q000166:cytology*; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology*; D013388:Succinimides / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000502:physiology*
C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D005452:Fluoresceins; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D013388:Succinimides; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase