Negative Regulation of Neural Stem/Progenitor Cell Proliferation by the Pten Tumor Suppressor Gene in Vivo

By M. Groszer, Rebecca Erickson, Deirdre D. Scripture-Adams, R. Lesche, A. Trumpp, J. Zack, H. Kornblum, Xin Liu, Hong Wu. Science, 2001

839 citations recorded by the source corpus.

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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/eda161c7a31f7537d430f00bbc38fc6b5d90bf1f

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Citations in the corpus

Patterns of neural stem and progenitor cell division may underlie evolutionary cortical expansion (2006, background): “Mice lacking Pten have enlarged, morphologically abnormal brains as the result of several actions, including increased cell proliferation, decreased cell death and enlarged cell siz”
Gli and hedgehog in cancer: tumours, embryos and stem cells (2002, background): “; Pten normally acts to restrict precursor proliferatio”
FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis (2009, background): “That FoxO deficiency leads to transient increase in cycling cells is not unanticipated based on previous studies with other PI3K pathway components wherein loss of the negative regulator PTEN was shown to result in sustained proliferative potential of NSCs (Groszer et al., 2001, 2006).”
Role for Akt3/Protein Kinase Bγ in Attainment of Normal Brain Size (2005, background): “Previous studies have demonstrated that the activation of Akt by the deletion of PTEN affects brain size (30, 37).”
The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism (2006, background): “Accordingly, tissue-specific deletion of PTEN leads to increased cell siz”
Brain tumour stem cells (2006, background): “PTEN is a tumour suppressor with an important function in the control of proliferation of neural stem cells and progenitor cells in vivo and in vitro”
iArc monogrAphs on the evAluAtion oF cArcinogenic risks to humAns (2012, background): “Pten deficiency in mice causes increases in cell proliferation, apoptotic resistance, stem-cell renewal/maintenance, centromeric instability, and DNA double-strand breaks (Groszer et al., 2001; Kimura et al., 2003; Wang et al., 2006; He et al., 2007; Shen et al., 2007), which can enhance susceptibil”
PTEN Deletion Enhances the Regenerative Ability of Adult Corticospinal Neurons (2010, background): “, in homozygous conditional Pten mutant ( Pten loxP/loxP ) mic”
Tenets of PTEN tumor suppression. (2008, background): “The first lines of evidence demonstrating that PTEN may also play a role in stem cell homeostasis came from the studies of Pten loss in murine neuronal tissues (Backman et al., 2001; Groszer et al., 2001; Kwon et al., 2001).”
Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. (2006, background): “…that PTEN and Notch exert during forebrain neurogenesis to maintain neural stem cells or progenitors in a proliferating undifferentiated state (Groszer et al., 2001; Sakamoto et al., 2003; Yoon and Gaiano, 2005), our findings suggest that aggressiveness of glioma growth may be largely…”
The cerebrospinal fluid provides a proliferative niche for neural progenitor cells (2011, methodology): “Here, we show that the apical complex protein Pals1 and Pten have opposing roles in localizing the Igf1R to the apical, ventricular domain of cerebral cortical progenitor cells.”