Dystrophin Deficiency Leads to Genomic Instability in Human
Pluripotent Stem Cells via NO Synthase-Induced Oxidative Stress

J 2019

Dystrophin Deficiency Leads to Genomic Instability in Human Pluripotent Stem Cells via NO Synthase-Induced Oxidative Stress

JELÍNKOVÁ, Šárka, Aneta KOHUTOVÁ, Petr FOJTÍK, Miriama KRUTÁ, Aleksandra VILOTIĆ et. al.

Basic information

Original name

Dystrophin Deficiency Leads to Genomic Instability in Human Pluripotent Stem Cells via NO Synthase-Induced Oxidative Stress

Authors

JELÍNKOVÁ, Šárka (203 Czech Republic, belonging to the institution), Aneta KOHUTOVÁ (703 Slovakia, belonging to the institution), Petr FOJTÍK (203 Czech Republic, belonging to the institution), Miriama KRUTÁ (703 Slovakia, belonging to the institution), Aleksandra VILOTIĆ (688 Serbia, belonging to the institution), Martin PEŠL (203 Czech Republic, belonging to the institution), Jan VRBSKÝ (203 Czech Republic), Renata GAILLYOVÁ (203 Czech Republic, belonging to the institution), Iveta VALÁŠKOVÁ (203 Czech Republic, belonging to the institution), Ivan FRÁK (703 Slovakia, belonging to the institution), Giancarlo FORTE (380 Italy), Petr DVOŘÁK (203 Czech Republic, belonging to the institution), Albano MELI (250 France, belonging to the institution), Vladimír ROTREKL (203 Czech Republic, guarantor, belonging to the institution), Lenka MARKOVÁ (203 Czech Republic, belonging to the institution), Tereza JURÁKOVÁ (203 Czech Republic, belonging to the institution) and Alain LACAMPAGNE (250 France)

Edition

Cells, Basel, MDPI, 2019, 2073-4409

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.366

RIV identification code

RIV/00216224:14110/19:00107273

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.3390/cells8010053

UT WoS

000459742400053

Keywords in English

DMD; dystrophin; pluripotent stem cells; genome stability; ROS; NO synthases

Abstract

V originále

Recent data on Duchenne muscular dystrophy (DMD) show myocyte progenitor’s involvement in the disease pathology often leading to the DMD patient’s death. The molecular mechanism underlying stem cell impairment in DMD has not been described. We created dystrophin-deficient human pluripotent stem cell (hPSC) lines by reprogramming cells from two DMD patients, and also by introducing dystrophin mutation into human embryonic stem cells via CRISPR/Cas9. While dystrophin is expressed in healthy hPSC, its deficiency in DMD hPSC lines induces the release of reactive oxygen species (ROS) through dysregulated activity of all three isoforms of nitric oxide synthase (further abrev. as, NOS). NOS-induced ROS release leads to DNA damage and genomic instability in DMD hPSC. We were able to reduce both the ROS release as well as DNA damage to the level of wild-type hPSC by inhibiting NOS activity.

Links

GBP302/12/G157, research and development project

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

Investor: Czech Science Foundation

MUNI/A/1087/2018, interní kód MU

Name: Molekulární a buněčná biologie pro biomedicínské vědy

Investor: Masaryk University, Category A

7AMB13FR011, research and development project

Name: Přeprogramování somatických buněk darovaných pacienty s dědičnou Duchennovou svalovou dystrofií do kardiomyocytů - nahlédnutí do molekulární podstaty patologických dějů u dilatační kardiomyopatie nemocných DMD (Acronym: DUCHENSTEM)

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

JELÍNKOVÁ, Šárka, Aneta KOHUTOVÁ, Petr FOJTÍK, Miriama KRUTÁ, Aleksandra VILOTIĆ, Martin PEŠL, Jan VRBSKÝ, Renata GAILLYOVÁ, Iveta VALÁŠKOVÁ, Ivan FRÁK, Giancarlo FORTE, Petr DVOŘÁK, Albano MELI, Vladimír ROTREKL, Lenka MARKOVÁ, Tereza JURÁKOVÁ and Alain LACAMPAGNE. Dystrophin Deficiency Leads to Genomic Instability in Human Pluripotent Stem Cells via NO Synthase-Induced Oxidative Stress. Cells. Basel: MDPI, 2019, vol. 8, No 1, p. 1-22. ISSN 2073-4409. Available from: https://dx.doi.org/10.3390/cells8010053.

@article{1498116,
   author = {Jelínková, Šárka and Kohutová, Aneta and Fojtík, Petr and Krutá, Miriama and Vilotić, Aleksandra and Pešl, Martin and Vrbský, Jan and Gaillyová, Renata and Valášková, Iveta and Frák, Ivan and Forte, Giancarlo and Dvořák, Petr and Meli, Albano and Rotrekl, Vladimír and Marková, Lenka and Juráková, Tereza and Lacampagne, Alain},
   article_location = {Basel},
   article_number = {1},
   doi = {http://dx.doi.org/10.3390/cells8010053},
   keywords = {DMD; dystrophin; pluripotent stem cells; genome stability; ROS; NO synthases},
   language = {eng},
   issn = {2073-4409},
   journal = {Cells},
   title = {Dystrophin Deficiency Leads to Genomic Instability in Human Pluripotent Stem Cells via NO Synthase-Induced Oxidative Stress},
   url = {http://dx.doi.org/10.3390/cells8010053},
   volume = {8},
   year = {2019}
}

TY  - JOUR
ID  - 1498116
AU  - Jelínková, Šárka - Kohutová, Aneta - Fojtík, Petr - Krutá, Miriama - Vilotić, Aleksandra - Pešl, Martin - Vrbský, Jan - Gaillyová, Renata - Valášková, Iveta - Frák, Ivan - Forte, Giancarlo - Dvořák, Petr - Meli, Albano - Rotrekl, Vladimír - Marková, Lenka - Juráková, Tereza - Lacampagne, Alain
PY  - 2019
TI  - Dystrophin Deficiency Leads to Genomic Instability in Human Pluripotent Stem Cells via NO Synthase-Induced Oxidative Stress
JF  - Cells
VL  - 8
IS  - 1
SP  - 1-22
EP  - 1-22
PB  - MDPI
SN  - 20734409
KW  - DMD
KW  - dystrophin
KW  - pluripotent stem cells
KW  - genome stability
KW  - ROS
KW  - NO synthases
UR  - http://dx.doi.org/10.3390/cells8010053
L2  - http://dx.doi.org/10.3390/cells8010053
N2  - Recent data on Duchenne muscular dystrophy (DMD) show myocyte progenitor’s involvement in the disease pathology often leading to the DMD patient’s death. The molecular mechanism underlying stem cell impairment in DMD has not been described. We created dystrophin-deficient human pluripotent stem cell (hPSC) lines by reprogramming cells from two DMD patients, and also by introducing dystrophin mutation into human embryonic stem cells via CRISPR/Cas9. While dystrophin is expressed in healthy hPSC, its deficiency in DMD hPSC lines induces the release of reactive oxygen species (ROS) through dysregulated activity of all three isoforms of nitric oxide synthase (further abrev. as, NOS). NOS-induced ROS release leads to DNA damage and genomic instability in DMD hPSC. We were able to reduce both the ROS release as well as DNA damage to the level of wild-type hPSC by inhibiting NOS activity.
ER  -

JELÍNKOVÁ, Šárka, Aneta KOHUTOVÁ, Petr FOJTÍK, Miriama KRUTÁ, Aleksandra VILOTI$\backslash$'C, Martin PEŠL, Jan VRBSKÝ, Renata GAILLYOVÁ, Iveta VALÁŠKOVÁ, Ivan FRÁK, Giancarlo FORTE, Petr DVOŘÁK, Albano MELI, Vladimír ROTREKL, Lenka MARKOVÁ, Tereza JURÁKOVÁ and Alain LACAMPAGNE. Dystrophin Deficiency Leads to Genomic Instability in Human Pluripotent Stem Cells via NO Synthase-Induced Oxidative Stress. \textit{Cells}. Basel: MDPI, 2019, vol.~8, No~1, p.~1-22. ISSN~2073-4409. Available from: https://dx.doi.org/10.3390/cells8010053.

Detailed Information on Publication Record