Gene Expression Profiling of Neural Stem Cells and Their Neuronal Progeny Reveals IGF2 as a Regulator of Adult Hippocampal Neurogenesis

被引:157
作者
Bracko, Oliver [2 ]
Singer, Tatjana [1 ]
Aigner, Stefan [1 ]
Knobloch, Marlen [2 ]
Winner, Beate [1 ]
Ray, Jasodhara [1 ]
Clemenson, Gregory D., Jr. [1 ]
Suh, Hoonkyo [1 ]
Couillard-Despres, Sebastien [3 ]
Aigner, Ludwig [3 ]
Gage, Fred H. [1 ]
Jessberger, Sebastian [2 ]
机构
[1] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA
[2] Swiss Fed Inst Technol, Inst Mol Hlth Sci, Dept Biol, CH-8093 Zurich, Switzerland
[3] Paracelsus Med Univ, Inst Mol Regenerat Med, A-5020 Salzburg, Austria
基金
瑞士国家科学基金会;
关键词
CENTRAL-NERVOUS-SYSTEM; GROWTH-FACTOR-II; DENTATE GYRUS; IN-VIVO; STEM/PROGENITOR CELLS; HETEROZYGOUS MICE; MAMMALIAN BRAIN; MOUSE BRAIN; INSULIN; PROLIFERATION;
D O I
10.1523/JNEUROSCI.4248-11.2012
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Neural stem cells (NSCs) generate neurons throughout life in the hippocampal dentate gyrus (DG). How gene expression signatures differ among NSCs and immature neurons remains largely unknown. We isolated NSCs and their progeny in the adult DG using transgenic mice expressing a GFP reporter under the control of the Sox2 promoter (labeling NSCs) and transgenic mice expressing a DsRed reporter under the control of the doublecortin (DCX) promoter (labeling immature neurons). Transcriptome analyses revealed distinct gene expression profiles between NSCs and immature neurons. Among the genes that were expressed at significantly higher levels in DG NSCs than in immature neurons was the growth factor insulin-like growth factor 2 (IGF2). We show that IGF2 selectively controls proliferation of DG NSCs in vitro and in vivo through AKT-dependent signaling. Thus, by gene expression profiling of NSCs and their progeny, we have identified IGF2 as a novel regulator of adult neurogenesis.
引用
收藏
页码:3376 / 3387
页数:12
相关论文
共 64 条
[1]   A hippocampal insulin-growth factor 2 pathway regulates the extinction of fear memories [J].
Agis-Balboa, Roberto Carlos ;
Arcos-Diaz, Dario ;
Wittnam, Jessica ;
Govindarajan, Nambirajan ;
Blom, Kim ;
Burkhardt, Susanne ;
Haladyniak, Ulla ;
Agbemenyah, Hope Yao ;
Zovoilis, Athanasios ;
Salinas-Riester, Gabriella ;
Opitz, Lennart ;
Sananbenesi, Farahnaz ;
Fischer, Andre .
EMBO JOURNAL, 2011, 30 (19) :4071-4083
[2]   Enriched Monolayer Precursor Cell Cultures from Micro-Dissected Adult Mouse Dentate Gyrus Yield Functional Granule Cell-Like Neurons [J].
Babu, Harish ;
Cheung, Giselle ;
Kettenmann, Helmut ;
Palmer, Theo D. ;
Kempermann, Gerd .
PLOS ONE, 2007, 2 (04)
[3]   In Vivo Fate Mapping and Expression Analysis Reveals Molecular Hallmarks of Prospectively Isolated Adult Neural Stem Cells [J].
Beckervordersandforth, Ruth ;
Tripathi, Pratibha ;
Ninkovic, Jovica ;
Bayam, Efil ;
Lepier, Alexandra ;
Stempfhuber, Barbara ;
Kirchhoff, Frank ;
Hirrlinger, Johannes ;
Haslinger, Anja ;
Lie, D. Chichung ;
Beckers, Johannes ;
Yoder, Bradley ;
Irmler, Martin ;
Goetz, Magdalena .
CELL STEM CELL, 2010, 7 (06) :744-758
[4]   Advances in protein kinase B signalling:: AKTion on multiple fronts [J].
Brazil, DP ;
Yang, ZZ ;
Hemmings, BA .
TRENDS IN BIOCHEMICAL SCIENCES, 2004, 29 (05) :233-242
[5]   Notch regulates cell fate and dendrite morphology of newborn neurons in the postnatal dentate gyrus [J].
Breunig, Joshua J. ;
Silbereis, John ;
Vaccarino, Flora M. ;
Sestan, Nenad ;
Rakic, Pasko .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (51) :20558-20563
[6]   Becoming a new neuron in the adult olfactory bulb [J].
Carleton, A ;
Petreanu, LT ;
Lansford, R ;
Alvarez-Buylla, A ;
Lledo, PM .
NATURE NEUROSCIENCE, 2003, 6 (05) :507-518
[7]   A critical role for IGF-II in memory consolidation and enhancement [J].
Chen, Dillon Y. ;
Stern, Sarah A. ;
Garcia-Osta, Ana ;
Saunier-Rebori, Bernadette ;
Pollonini, Gabriella ;
Bambah-Mukku, Dhananjay ;
Blitzer, Robert D. ;
Alberini, Cristina M. .
NATURE, 2011, 469 (7331) :491-U63
[8]   miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche [J].
Cheng, Li-Chun ;
Pastrana, Erika ;
Tavazoie, Masoud ;
Doetsch, Fiona .
NATURE NEUROSCIENCE, 2009, 12 (04) :399-408
[9]   Insulin-like Growth Factor 2 Is Required for Progression to Advanced Medulloblastoma in patched1 Heterozygous Mice [J].
Corcoran, Ryan B. ;
Raveh, Tal Bachar ;
Barakat, Monique T. ;
Lee, Eunice Y. ;
Scott, Matthew P. .
CANCER RESEARCH, 2008, 68 (21) :8788-8795
[10]   Doublecortin expression levels in adult brain reflect neurogenesis [J].
Couillard-Despres, S ;
Winner, B ;
Schaubeck, S ;
Aigner, R ;
Vroemen, M ;
Weidner, N ;
Bogdahn, U ;
Winkler, J ;
Kuhn, HG ;
Aigner, L .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2005, 21 (01) :1-14