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

Nguyen, T. D., Widera, D. ORCID: https://orcid.org/0000-0003-1686-130X, Greiner, J., Müller, J., Martin, I., Slotta, C., Hauser, S., Kaltschmidt, C. and Kaltschmidt, B. (2013) Prolonged cultivation of hippocampal neural precursor cells shifts their differentiation potential and selects for aneuploid cells. Biological chemistry, 394 (12). pp. 1623-1636. ISSN 1437-4315 doi: 10.1515/hsz-2013-0191

Abstract/Summary

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.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/39520
Identification Number/DOI	10.1515/hsz-2013-0191
Refereed	Yes
Divisions	No Reading authors. Back catalogue items Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
Publisher	De Gruyter
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