Abstract
Fanconi anaemia (FA) is a recessive disorder characterized by genomic instability, congenital abnormalities, cancer predisposition and bone marrow (BM) failure. However, the pathogenesis of FA is not fully understood partly due to the limitations of current disease models. Here, we derive integration free-induced pluripotent stem cells (iPSCs) from an FA patient without genetic complementation and report in situ gene correction in FA-iPSCs as well as the generation of isogenic FANCA-deficient human embryonic stem cell (ESC) lines. FA cellular phenotypes are recapitulated in iPSCs/ESCs and their adult stem/progenitor cell derivatives. By using isogenic pathogenic mutation-free controls as well as cellular and genomic tools, our model serves to facilitate the discovery of novel disease features. We validate our model as a drug-screening platform by identifying several compounds that improve hematopoietic differentiation of FA-iPSCs. These compounds are also able to rescue the hematopoietic phenotype of FA patient BM cells.
| Original language | English |
|---|---|
| Article number | 4330 |
| Journal | Nature Communications |
| Volume | 5 |
| DOIs | |
| Publication status | Published - Jul 7 2014 |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Chemistry(all)
- Physics and Astronomy(all)
Cite this
Modelling Fanconi anemia pathogenesis and therapeutics using integration-free patient-derived iPSCs. / Liu, Guang Hui; Suzuki, Keiichiro; Li, Mo; Qu, Jing; Montserrat, Nuria; Tarantino, Carolina; Gu, Ying; Yi, Fei; Xu, Xiuling; Zhang, Weiqi; Ruiz, Sergio; Plongthongkum, Nongluk; Zhang, Kun; Masuda, Shigeo; Nivet, Emmanuel; Tsunekawa, Yuji; Soligalla, Rupa Devi; Goebl, April; Aizawa, Emi; Kim, Na Young; Kim, Jessica; Dubova, Ilir; Li, Ying; Ren, Ruotong; Benner, Chris; Del Sol, Antonio; Bueren, Juan; Trujillo, Juan Pablo; Surralles, Jordi; Cappelli, Enrico; Dufour, Carlo; Esteban, Concepcion Rodriguez; Belmonte, Juan Carlos Izpisua.
In: Nature Communications, Vol. 5, 4330, 07.07.2014.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Modelling Fanconi anemia pathogenesis and therapeutics using integration-free patient-derived iPSCs
AU - Liu, Guang Hui
AU - Suzuki, Keiichiro
AU - Li, Mo
AU - Qu, Jing
AU - Montserrat, Nuria
AU - Tarantino, Carolina
AU - Gu, Ying
AU - Yi, Fei
AU - Xu, Xiuling
AU - Zhang, Weiqi
AU - Ruiz, Sergio
AU - Plongthongkum, Nongluk
AU - Zhang, Kun
AU - Masuda, Shigeo
AU - Nivet, Emmanuel
AU - Tsunekawa, Yuji
AU - Soligalla, Rupa Devi
AU - Goebl, April
AU - Aizawa, Emi
AU - Kim, Na Young
AU - Kim, Jessica
AU - Dubova, Ilir
AU - Li, Ying
AU - Ren, Ruotong
AU - Benner, Chris
AU - Del Sol, Antonio
AU - Bueren, Juan
AU - Trujillo, Juan Pablo
AU - Surralles, Jordi
AU - Cappelli, Enrico
AU - Dufour, Carlo
AU - Esteban, Concepcion Rodriguez
AU - Belmonte, Juan Carlos Izpisua
PY - 2014/7/7
Y1 - 2014/7/7
N2 - Fanconi anaemia (FA) is a recessive disorder characterized by genomic instability, congenital abnormalities, cancer predisposition and bone marrow (BM) failure. However, the pathogenesis of FA is not fully understood partly due to the limitations of current disease models. Here, we derive integration free-induced pluripotent stem cells (iPSCs) from an FA patient without genetic complementation and report in situ gene correction in FA-iPSCs as well as the generation of isogenic FANCA-deficient human embryonic stem cell (ESC) lines. FA cellular phenotypes are recapitulated in iPSCs/ESCs and their adult stem/progenitor cell derivatives. By using isogenic pathogenic mutation-free controls as well as cellular and genomic tools, our model serves to facilitate the discovery of novel disease features. We validate our model as a drug-screening platform by identifying several compounds that improve hematopoietic differentiation of FA-iPSCs. These compounds are also able to rescue the hematopoietic phenotype of FA patient BM cells.
AB - Fanconi anaemia (FA) is a recessive disorder characterized by genomic instability, congenital abnormalities, cancer predisposition and bone marrow (BM) failure. However, the pathogenesis of FA is not fully understood partly due to the limitations of current disease models. Here, we derive integration free-induced pluripotent stem cells (iPSCs) from an FA patient without genetic complementation and report in situ gene correction in FA-iPSCs as well as the generation of isogenic FANCA-deficient human embryonic stem cell (ESC) lines. FA cellular phenotypes are recapitulated in iPSCs/ESCs and their adult stem/progenitor cell derivatives. By using isogenic pathogenic mutation-free controls as well as cellular and genomic tools, our model serves to facilitate the discovery of novel disease features. We validate our model as a drug-screening platform by identifying several compounds that improve hematopoietic differentiation of FA-iPSCs. These compounds are also able to rescue the hematopoietic phenotype of FA patient BM cells.
UR - http://www.scopus.com/inward/record.url?scp=84903979340&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84903979340&partnerID=8YFLogxK
U2 - 10.1038/ncomms5330
DO - 10.1038/ncomms5330
M3 - Article
C2 - 24999918
AN - SCOPUS:84903979340
VL - 5
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 4330
ER -