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 and Juan Carlos Izpisua Belmonte ()
Additional contact information
Guang-Hui Liu: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Keiichiro Suzuki: Gene Expression Laboratory, Salk Institute for Biological Studies
Mo Li: Gene Expression Laboratory, Salk Institute for Biological Studies
Jing Qu: Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences
Nuria Montserrat: Center for Regenerative Medicine in Barcelona
Carolina Tarantino: Center for Regenerative Medicine in Barcelona
Ying Gu: Gene Expression Laboratory, Salk Institute for Biological Studies
Fei Yi: Gene Expression Laboratory, Salk Institute for Biological Studies
Xiuling Xu: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Weiqi Zhang: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Sergio Ruiz: Gene Expression Laboratory, Salk Institute for Biological Studies
Nongluk Plongthongkum: University of California at San Diego
Kun Zhang: University of California at San Diego
Shigeo Masuda: Gene Expression Laboratory, Salk Institute for Biological Studies
Emmanuel Nivet: Gene Expression Laboratory, Salk Institute for Biological Studies
Yuji Tsunekawa: Gene Expression Laboratory, Salk Institute for Biological Studies
Rupa Devi Soligalla: Gene Expression Laboratory, Salk Institute for Biological Studies
April Goebl: Gene Expression Laboratory, Salk Institute for Biological Studies
Emi Aizawa: Gene Expression Laboratory, Salk Institute for Biological Studies
Na Young Kim: Gene Expression Laboratory, Salk Institute for Biological Studies
Jessica Kim: Gene Expression Laboratory, Salk Institute for Biological Studies
Ilir Dubova: Gene Expression Laboratory, Salk Institute for Biological Studies
Ying Li: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Ruotong Ren: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Chris Benner: Integrative Genomics and Bioinformatics Core, Salk Institute for Biological Studies
Antonio del Sol: Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg
Juan Bueren: Medioambientales y Tecnológicas (CIEMAT)/Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER)
Juan Pablo Trujillo: Universitat Autonoma de Barcelona, Campus de Bellaterra s/n 08193 Bellaterra
Jordi Surralles: Universitat Autonoma de Barcelona, Campus de Bellaterra s/n 08193 Bellaterra
Enrico Cappelli: Clinical and Experimental Hematology Unit, G. Gaslini Children’s Hospital
Carlo Dufour: Clinical and Experimental Hematology Unit, G. Gaslini Children’s Hospital
Concepcion Rodriguez Esteban: Gene Expression Laboratory, Salk Institute for Biological Studies
Juan Carlos Izpisua Belmonte: Gene Expression Laboratory, Salk Institute for Biological Studies

Nature Communications, 2014, vol. 5, issue 1, 1-17

Abstract: 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.

Date: 2014
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms5330 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5330

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms5330

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().