Mutation Frequency Dynamics in HPRT Locus in Culture-Adapted Human Embryonic Stem Cells and Induced Pluripotent Stem Cells Correspond to Their Differentiated Counterparts

0435415 - BFÚ 2015 RIV US eng J - Článek v odborném periodiku
Krutá, M. - Seneklová, M. - Raška, J. - Salykin, A. - Zerzánková, L. - Pešl, M. - Bártová, Eva - Franek, Michal … celkem 14 autorů
Mutation Frequency Dynamics in HPRT Locus in Culture-Adapted Human Embryonic Stem Cells and Induced Pluripotent Stem Cells Correspond to Their Differentiated Counterparts.
Stem Cells and Development. Roč. 23, č. 20 (2014), s. 2443-2454. ISSN 1547-3287. E-ISSN 1557-8534
Grant CEP: GA ČR(CZ) GBP302/12/G157; GA MŠMT(CZ) ED1.100/02/0123
Institucionální podpora: RVO:68081707
Klíčová slova: BASE EXCISION-REPAIR * HUMAN SOMATIC-CELLS * X-INACTIVATION
Kód oboru RIV: BO - Biofyzika
Impakt faktor: 3.727, rok: 2014

The genomic destabilization associated with the adaptation of human embryonic stem cells (hESCs) to culture conditions or the reprogramming of induced pluripotent stem cells (iPSCs) increases the risk of tumorigenesis upon the clinical use of these cells and decreases their value as a model for cell biology studies. Base excision repair (BER), a major genomic integrity maintenance mechanism, has been shown to fail during hESC adaptation. Here, we show that the increase in the mutation frequency (MF) caused by the inhibition of BER was similar to that caused by the hESC adaptation process. The increase in MF reflected the failure of DNA maintenance mechanisms and the subsequent increase in MF rather than being due solely to the accumulation of mutants over a prolonged period, as was previously suggested. The increase in the ionizing-radiation-induced MF in adapted hESCs exceeded the induced MF in nonadapted hESCs and differentiated cells.
Trvalý link: http://hdl.handle.net/11104/0239299