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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

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Volume 394, Issue 12

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Prolonged cultivation of hippocampal neural precursor cells shifts their differentiation potential and selects for aneuploid cells

The Duy Nguyen
  • Molecular Neurobiology, Department of Cell Biology, Faculty of Biology, University of Bielefeld, Universitätsstrasse 25, D-33501 Bielefeld, Germany
  • These authors contributed equally to this work.
  • Other articles by this author:
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/ Darius Widera
  • Department of Cell Biology, Faculty of Biology, University of Bielefeld, Universitätsstrasse 25, D-33501 Bielefeld, Germany
  • These authors contributed equally to this work.
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/ Johannes Greiner
  • Department of Cell Biology, Faculty of Biology, University of Bielefeld, Universitätsstrasse 25, D-33501 Bielefeld, Germany
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/ Janine Müller
  • Molecular Neurobiology, Department of Cell Biology, Faculty of Biology, University of Bielefeld, Universitätsstrasse 25, D-33501 Bielefeld, Germany
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/ Ina Martin
  • Molecular Neurobiology, Department of Cell Biology, Faculty of Biology, University of Bielefeld, Universitätsstrasse 25, D-33501 Bielefeld, Germany
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/ Carsten Slotta
  • Molecular Neurobiology, Department of Cell Biology, Faculty of Biology, University of Bielefeld, Universitätsstrasse 25, D-33501 Bielefeld, Germany
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/ Stefan Hauser
  • Molecular Neurobiology, Department of Cell Biology, Faculty of Biology, University of Bielefeld, Universitätsstrasse 25, D-33501 Bielefeld, Germany
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/ Christian Kaltschmidt
  • Department of Cell Biology, Faculty of Biology, University of Bielefeld, Universitätsstrasse 25, D-33501 Bielefeld, Germany
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  • De Gruyter OnlineGoogle Scholar
/ Barbara Kaltschmidt
  • Corresponding author
  • Molecular Neurobiology, Department of Cell Biology, Faculty of Biology, University of Bielefeld, Universitätsstrasse 25, D-33501 Bielefeld, Germany
  • Email
  • Other articles by this author:
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Published Online: 2013-10-01 | DOI: https://doi.org/10.1515/hsz-2013-0191

Abstract

Neural precursor cells (NPCs) are lineage-restricted neural stem cells with limited self-renewal, giving rise to a broad range of neural cell types such as neurons, astrocytes, and oligodendrocytes. Despite this developmental potential, the differentiation capacity of NPCs has been controversially discussed concerning the trespassing lineage boundaries, for instance resulting in hematopoietic competence. Assessing their in vitro plasticity, we isolated nestin+/Sox2+, NPCs from the adult murine hippocampus. In vitro-expanded adult NPCs were able to form neurospheres, self-renew, and differentiate into neuronal, astrocytic, and oligodendrocytic cells. Although NPCs cultivated in early passage efficiently gave rise to neuronal cells in a directed differentiation assay, extensively cultivated NPCs revealed reduced potential for ectodermal differentiation. We further observed successful differentiation of long-term cultured NPCs into osteogenic and adipogenic cell types, suggesting that NPCs underwent a fate switch during culture. NPCs cultivated for more than 12 passages were aneuploid (abnormal chromosome numbers such as 70 chromosomes). Furthermore, they showed growth factor-independent proliferation, a hallmark of tumorigenic transformation. In conclusion, our findings substantiate the lineage restriction of NPCs from adult mammalian hippocampus. Prolonged cultivation results, however, in enhanced differentiation potential, which may be attributed to transformation events leading to aneuploid cells.

Keywords: cellular transformation; hippocampus; neural precursor cells; neural stem cells; stem cell plasticity

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About the article

Corresponding author: Barbara Kaltschmidt, Molecular Neurobiology, Department of Cell Biology, Faculty of Biology, University of Bielefeld, Universitätsstrasse 25, D-33501 Bielefeld, Germany, e-mail:


Received: 2013-05-24

Accepted: 2013-09-27

Published Online: 2013-10-01

Published in Print: 2013-12-01


Citation Information: Biological Chemistry, Volume 394, Issue 12, Pages 1623–1636, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2013-0191.

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