Universität zu Köln

Mehrjardi, Narges Zare, Molcanyi, Marek, Hatay, Firuze Fulya, Timmer, Marco, Shahbazi, Ebrahim, Ackermann, Justus P., Herms, Stefan, Heilmann-Heimbach, Stefanie, Wunderlich, Thomas F., Prochnow, Nora, Haghikia, Aiden, Lampert, Angelika ORCID: 0000-0001-6319-6272, Hescheler, Juergen, Neugebauer, Edmund A. M., Baharvand, Hossein and Saric, Tomo (2020). Acquisition of chromosome 1q duplication in parental and genome-edited human-induced pluripotent stem cell-derived neural stem cells results in their higher proliferation rate in vitro and in vivo. Cell Prolif., 53 (10). HOBOKEN: WILEY. ISSN 1365-2184

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Abstract

Objectives Genetic engineering of human-induced pluripotent stem cell-derived neural stem cells (hiPSC-NSC) may increase the risk of genomic aberrations. Therefore, we asked whether genetic modification of hiPSC-NSCs exacerbates chromosomal abnormalities that may occur during passaging and whether they may cause any functional perturbations in NSCs in vitro and in vivo. Materials and Methods The transgenic cassette was inserted into the AAVS1 locus, and the genetic integrity of zinc-finger nuclease (ZFN)-modified hiPSC-NSCs was assessed by the SNP-based karyotyping. The hiPSC-NSC proliferation was assessed in vitro by the EdU incorporation assay and in vivo by staining of brain slices with Ki-67 antibody at 2 and 8 weeks after transplantation of ZFN-NSCs with and without chromosomal aberration into the striatum of immunodeficient rats. Results During early passages, no chromosomal abnormalities were detected in unmodified or ZFN-modified hiPSC-NSCs. However, at higher passages both cell populations acquired duplication of the entire long arm of chromosome 1, dup(1)q. ZNF-NSCs carrying dup(1)q exhibited higher proliferation rate than karyotypically intact cells, which was partly mediated by increased expression ofAKT3located on Chr1q. Compared to karyotypically normal ZNF-NSCs, cells with dup(1)q also exhibited increased proliferation in vivo 2 weeks, but not 2 months, after transplantation. Conclusions These results demonstrate that, independently of ZFN-editing, hiPSC-NSCs have a propensity for acquiring dup(1)q and this aberration results in increased proliferation which might compromise downstream hiPSC-NSC applications.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mehrjardi, Narges Zare UNSPECIFIED UNSPECIFIED UNSPECIFIED Molcanyi, Marek UNSPECIFIED UNSPECIFIED UNSPECIFIED Hatay, Firuze Fulya UNSPECIFIED UNSPECIFIED UNSPECIFIED Timmer, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Shahbazi, Ebrahim UNSPECIFIED UNSPECIFIED UNSPECIFIED Ackermann, Justus P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Herms, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Heilmann-Heimbach, Stefanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Wunderlich, Thomas F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Prochnow, Nora UNSPECIFIED UNSPECIFIED UNSPECIFIED Haghikia, Aiden UNSPECIFIED UNSPECIFIED UNSPECIFIED Lampert, Angelika UNSPECIFIED orcid.org/0000-0001-6319-6272 UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Neugebauer, Edmund A. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Baharvand, Hossein UNSPECIFIED UNSPECIFIED UNSPECIFIED Saric, Tomo UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-319267
DOI:	10.1111/cpr.12892
Journal or Publication Title:	Cell Prolif.
Volume:	53
Number:	10
Date:	2020
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1365-2184
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EDITING SYSTEM; INSTABILITY; DIFFERENTIATION; ABERRATIONS; EXPRESSION; STABILITY; HYBRIDIZATION; ANEUPLOIDY; CULTURE; GENES Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/31926