Oncotarget

Research Papers:

Gene amplification during differentiation of mammalian neural stem cells in vitro and in vivo

Ulrike Fischer _, Christina Backes, Abdulrahman Raslan, Andreas Keller, Carola Meier and Eckart Meese

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Oncotarget. 2015; 6:7023-7039. https://doi.org/10.18632/oncotarget.3248

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Abstract

Ulrike Fischer1, Christina Backes1,3, Abdulrahman Raslan2, Andreas Keller3, Carola Meier2, Eckart Meese1

1Department of Human Genetics, Saarland University, 66421 Homburg/Saar, Germany

2Department of Anatomy and Cell Biology, Saarland University, 66421 Homburg/Saar, Germany

3Clinical Bioinformatics, Saarland University, 66123 Saarbrücken, Germany

Correspondence to:

Ulrike Fischer, e-mail: ulrike.fischer@uks.eu

Keywords: neurosphere, genomic stability, in vivo, array-CGH

Received: November 04, 2014     Accepted: January 28, 2015     Published: February 19, 2015

ABSTRACT

In development of amphibians and flies, gene amplification is one of mechanisms to increase gene expression. In mammalian cells, gene amplification seems to be restricted to tumorigenesis and acquiring of drug-resistance in cancer cells. Here, we report a complex gene amplification pattern in mouse neural progenitor cells during differentiation with approximately 10% of the genome involved. Half of the amplified mouse chromosome regions overlap with amplified regions previously reported in human neural progenitor cells, indicating conserved mechanisms during differentiation. Using fluorescence in situ hybridization, we verified the amplification in single cells of primary mouse mesencephalon E14 (embryonic stage) neurosphere cells during differentiation. In vivo we confirmed gene amplifications of the TRP53 gene in cryosections from mouse embryos at stage E11.5. Gene amplification is not only a cancer-related mechanism but is also conserved in evolution, occurring during differentiation of mammalian neural stem cells


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