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

  • The Duy Nguyen , Darius Widera , Johannes Greiner , Janine Müller , Ina Martin , Carsten Slotta , Stefan Hauser , Christian Kaltschmidt and Barbara Kaltschmidt EMAIL logo
Published/Copyright: October 1, 2013
Biological Chemistry
From the journal Biological Chemistry Volume 394 Issue 12

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

We thank Angela Kralemann-Köhler and Vivien Krell for the excellent technical help and Timo Schomann, Lena-Marie Grunwald, and Ilse Betzendahl for the karyotyping. Experimental work described herein that was performed in our laboratory was supported by a grant of University of Bielefeld to D.W., grants of the German Research Council (DFG) to C.K., and a grant of the German Ministry of Research and Education (BMBF) to B.K. The β-catenin monoclonal antibody developed by J. Balsamo and J. Lilien was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by the Department of Biology, University of Iowa, Iowa City, IA, USA.

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Received: 2013-5-24
Accepted: 2013-9-27
Published Online: 2013-10-01
Published in Print: 2013-12-01

©2013 by Walter de Gruyter Berlin Boston

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  1. Masthead
  2. Masthead
  3. Guest Editorial
  4. Highlight: perspectives in molecular neurobiology
  5. HIGHLIGHT: PERSPECTIVES IN MOLECULAR NEUROBIOLOGY
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https://doi.org/10.1515/hsz-2013-0191
Keywords for this article
cellular transformation; hippocampus; neural precursor cells; neural stem cells; stem cell plasticity

Articles in the same Issue

  1. Masthead
  2. Masthead
  3. Guest Editorial
  4. Highlight: perspectives in molecular neurobiology
  5. HIGHLIGHT: PERSPECTIVES IN MOLECULAR NEUROBIOLOGY
  6. Role of the peroxisome proliferator-activated receptors (PPAR)-α, β/δ and γ triad in regulation of reactive oxygen species signaling in brain
  7. Molecular triggers of neuroinflammation in mouse models of demyelinating diseases
  8. Sox appeal – Sox10 attracts epigenetic and transcriptional regulators in myelinating glia
  9. MeCP2 phosphorylation in the brain: from transcription to behavior
  10. The nuclear receptor peroxisome proliferator-activated receptor-γ promotes oligodendrocyte differentiation through mechanisms involving mitochondria and oscillatory Ca2+ waves
  11. G-protein-coupled designer receptors – new chemical-genetic tools for signal transduction research
  12. Prolonged cultivation of hippocampal neural precursor cells shifts their differentiation potential and selects for aneuploid cells
  13. Reviews
  14. Eternity and functionality – rational access to physiologically relevant cell lines
  15. Structural and functional insights into the Spir/formin actin nucleator complex
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