Modelling Fanconi anemia pathogenesis and therapeutics using integration-free patient-derived iPSCs

Guang Hui Liu; Keiichiro Suzuki; Mo Li; Jing Qu; Nuria Montserrat; Carolina Tarantino; Ying Gu; Fei Yi; Xiuling Xu; Weiqi Zhang; Sergio Ruiz; Nongluk Plongthongkum; Kun Zhang; Shigeo Masuda; Emmanuel Nivet; Yuji Tsunekawa; Rupa Devi Soligalla; April Goebl; Emi Aizawa; Na Young Kim; Jessica Kim; Ilir Dubova; Ying Li; Ruotong Ren; Chris Benner; Antonio Del Sol; Juan Bueren; Juan Pablo Trujillo; Jordi Surralles; Enrico Cappelli; Carlo Dufour; Concepcion Rodriguez Esteban; Juan Carlos Izpisua Belmonte

doi:10.1038/ncomms5330

Modelling Fanconi anemia pathogenesis and therapeutics using integration-free patient-derived iPSCs

Guang Hui Liu, Keiichiro Suzuki, Mo Li, Jing Qu, Nuria Montserrat, Carolina Tarantino, Ying Gu, Fei Yi, Xiuling Xu, Weiqi Zhang, Sergio Ruiz, Nongluk Plongthongkum, Kun Zhang, Shigeo Masuda, Emmanuel Nivet, Yuji Tsunekawa, Rupa Devi Soligalla, April Goebl, Emi Aizawa, Na Young KimJessica Kim, Ilir Dubova, Ying Li, Ruotong Ren, Chris Benner, Antonio Del Sol, Juan Bueren, Juan Pablo Trujillo, Jordi Surralles, Enrico Cappelli, Carlo Dufour, Concepcion Rodriguez Esteban, Juan Carlos Izpisua Belmonte

Istituto "Giannina Gaslini"

Research output: Contribution to journal › Article › peer-review

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	https://doi.org/10.1038/ncomms5330
Publication status	Published - Jul 7 2014

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Chemistry(all)
Physics and Astronomy(all)

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Liu, G. H., Suzuki, K., Li, M., Qu, J., Montserrat, N., Tarantino, C., Gu, Y., Yi, F., Xu, X., Zhang, W., Ruiz, S., Plongthongkum, N., Zhang, K., Masuda, S., Nivet, E., Tsunekawa, Y., Soligalla, R. D., Goebl, A., Aizawa, E., ... Belmonte, J. C. I. (2014). Modelling Fanconi anemia pathogenesis and therapeutics using integration-free patient-derived iPSCs. Nature Communications, 5, [4330]. https://doi.org/10.1038/ncomms5330

Liu, GH, Suzuki, K, Li, M, Qu, J, Montserrat, N, Tarantino, C, Gu, Y, Yi, F, Xu, X, Zhang, W, Ruiz, S, Plongthongkum, N, Zhang, K, Masuda, S, Nivet, E, Tsunekawa, Y, Soligalla, RD, Goebl, A, Aizawa, E, Kim, NY, Kim, J, Dubova, I, Li, Y, Ren, R, Benner, C, Del Sol, A, Bueren, J, Trujillo, JP, Surralles, J, Cappelli, E, Dufour, C, Esteban, CR & Belmonte, JCI 2014, 'Modelling Fanconi anemia pathogenesis and therapeutics using integration-free patient-derived iPSCs', Nature Communications, vol. 5, 4330. https://doi.org/10.1038/ncomms5330

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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.",

author = "Liu, {Guang Hui} and Keiichiro Suzuki and Mo Li and Jing Qu and Nuria Montserrat and Carolina Tarantino and Ying Gu and Fei Yi and Xiuling Xu and Weiqi Zhang and Sergio Ruiz and Nongluk Plongthongkum and Kun Zhang and Shigeo Masuda and Emmanuel Nivet and Yuji Tsunekawa and Soligalla, {Rupa Devi} and April Goebl and Emi Aizawa and Kim, {Na Young} and Jessica Kim and Ilir Dubova and Ying Li and Ruotong Ren and Chris Benner and {Del Sol}, Antonio and Juan Bueren and Trujillo, {Juan Pablo} and Jordi Surralles and Enrico Cappelli and Carlo Dufour and Esteban, {Concepcion Rodriguez} and Belmonte, {Juan Carlos Izpisua}",

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AU - Liu, Guang Hui

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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

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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

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Modelling Fanconi anemia pathogenesis and therapeutics using integration-free patient-derived iPSCs

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