Mutation frequency dynamics in HPRT locus in culture adapted
hESCs and iPSCs correspond to their differentiated counterparts

J 2014

Mutation frequency dynamics in HPRT locus in culture adapted hESCs and iPSCs correspond to their differentiated counterparts

KRUTÁ, Miriama; Monika ŠENEKLOVÁ; Jan RAŠKA; Anton SALYKIN; Lenka ZERZÁNKOVÁ et al.

Základní údaje

Originální název

Mutation frequency dynamics in HPRT locus in culture adapted hESCs and iPSCs correspond to their differentiated counterparts

Autoři

Vydání

Stem Cells and Development, Mary Ann Liebert, Inc. 2014, 1547-3287

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

Genetika a molekulární biologie

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 3.727

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/14:00073651

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

mutation frequency; human embryonic stem cells; induced pluripotent stem cells; hypoxanthine phosphoribosyltransferase; base excision repair; apurinic/apyrimidinic endonuclease

Štítky

EL OK

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 10. 11. 2014 14:18, Ing. Mgr. Věra Pospíšilíková

Anotace

V originále

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 non-adapted hESCs and differentiated cells. Unlike hESCs, the overall DNA maintenance in iPSCs, which was reflected by the MF, was similar to that in differentiated cells regardless of the time spent in culture and despite the upregulation of several genes responsible for genome maintenance during the reprogramming process. Taken together, our results suggest that the changes in BER activity during the long-term cultivation of hESCs increase the mutagenic burden, whereas neither reprogramming nor long-term propagation in culture changes the MF in iPSCs.

Návaznosti

EE2.3.30.0009, projekt VaV

Název: Zaměstnáním čerstvých absolventů doktorského studia k vědecké excelenci

GA13-19910S, projekt VaV

Název: Studium dilatační kardiomyopatie spojené s Duchenovou svalovou dystrofií na modelové tkáni tvořené kardiomyocyty derivovanými z iPS buněk

Investor: Grantová agentura ČR, Studium dilatační kardiomyopatie spojené s Duchenovou svalovou dystrofií na modelové tkáni tvořené kardiomyocyty derivovanými z iPS buněk

GBP302/12/G157, projekt VaV

Název: Dynamika a organizace chromosomů během buněčného cyklu a při diferenciaci v normě a patologii

Investor: Grantová agentura ČR, Dynamika a organizace chromosomů během buněčného cyklu a při diferenciaci v normě a patologii

MSM0021622430, záměr

Název: Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie

Citovat

KRUTÁ, Miriama; Monika ŠENEKLOVÁ; Jan RAŠKA; Anton SALYKIN; Lenka ZERZÁNKOVÁ; Martin PEŠL; Eva BÁRTOVÁ; Michal FRANEK; Aneta BAUMEISTEROVÁ; Stanislava KOŠKOVÁ; Kai J. NEELSEN; Aleš HAMPL; Petr DVOŘÁK a Vladimír ROTREKL. Mutation frequency dynamics in HPRT locus in culture adapted hESCs and iPSCs correspond to their differentiated counterparts. Stem Cells and Development. Mary Ann Liebert, Inc., 2014, roč. 23, č. 20, s. 2443-2454. ISSN 1547-3287. Dostupné z: https://doi.org/10.1089/scd.2013.0611.

@article{1184053,
   author = {Krutá, Miriama and Šeneklová, Monika and Raška, Jan and Salykin, Anton and Zerzánková, Lenka and Pešl, Martin and Bártová, Eva and Franek, Michal and Baumeisterová, Aneta and Košková, Stanislava and Neelsen, Kai J. and Hampl, Aleš and Dvořák, Petr and Rotrekl, Vladimír},
   article_number = {20},
   doi = {https://doi.org/10.1089/scd.2013.0611},
   keywords = {mutation frequency; human embryonic stem cells; induced pluripotent stem cells; hypoxanthine phosphoribosyltransferase; base excision repair; apurinic/apyrimidinic endonuclease},
   language = {eng},
   issn = {1547-3287},
   journal = {Stem Cells and Development},
   title = {Mutation frequency dynamics in HPRT locus in culture adapted hESCs and iPSCs correspond to their differentiated counterparts},
   volume = {23},
   year = {2014}
}

TY  - JOUR
ID  - 1184053
AU  - Krutá, Miriama - Šeneklová, Monika - Raška, Jan - Salykin, Anton - Zerzánková, Lenka - Pešl, Martin - Bártová, Eva - Franek, Michal - Baumeisterová, Aneta - Košková, Stanislava - Neelsen, Kai J. - Hampl, Aleš - Dvořák, Petr - Rotrekl, Vladimír
PY  - 2014
TI  - Mutation frequency dynamics in HPRT locus in culture adapted hESCs and iPSCs correspond to their differentiated counterparts
JF  - Stem Cells and Development
VL  - 23
IS  - 20
SP  - 2443-2454
EP  - 2443-2454
PB  - Mary Ann Liebert, Inc.
SN  - 15473287
KW  - mutation frequency
KW  - human embryonic stem cells
KW  - induced pluripotent stem cells
KW  - hypoxanthine phosphoribosyltransferase
KW  - base excision repair
KW  - apurinic/apyrimidinic endonuclease
N2  - 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 non-adapted hESCs and differentiated cells. Unlike hESCs, the overall DNA maintenance in iPSCs, which was reflected by the MF, was similar to that in differentiated cells regardless of the time spent in culture and despite the upregulation of several genes responsible for genome maintenance during the reprogramming process. Taken together, our results suggest that the changes in BER activity during the long-term cultivation of hESCs increase the mutagenic burden, whereas neither reprogramming nor long-term propagation in culture changes the MF in iPSCs.
ER  -

KRUTÁ, Miriama; Monika ŠENEKLOVÁ; Jan RAŠKA; Anton SALYKIN; Lenka ZERZÁNKOVÁ; Martin PEŠL; Eva BÁRTOVÁ; Michal FRANEK; Aneta BAUMEISTEROVÁ; Stanislava KOŠKOVÁ; Kai J. NEELSEN; Aleš HAMPL; Petr DVOŘÁK a Vladimír ROTREKL. Mutation frequency dynamics in HPRT locus in culture adapted hESCs and iPSCs correspond to their differentiated counterparts. \textit{Stem Cells and Development}. Mary Ann Liebert, Inc., 2014, roč.~23, č.~20, s.~2443-2454. ISSN~1547-3287. Dostupné z: https://doi.org/10.1089/scd.2013.0611.

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