Journal
NATURE COMMUNICATIONS
Volume 5, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms5330
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Funding
- National Basic Research Program of China (973 Program) [2014CB964600, 2014CB910500]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA01020312]
- NSFC [81271266, 31222039, 81330008, 31201111, 81371342, 81300261, 81300677]
- Key Research Program of the Chinese Academy of Sciences [KJZDEW-TZ-L05]
- Beijing Natural Science Foundation [7141005, 5142016]
- Thousand Young Talents program of China
- National Laboratory of Biomacromolecules [012kf02, 2013kf05, 2013kf11, 2014kf02]
- State Key Laboratory of Drug Research [SIMM1302KF-17]
- CIRM fellowship
- La Fundacio Privada La Marato de TV3 [121430/31/32]
- Spanish Ministry of Economy and Competitiveness [PLE 2009-0164]
- Uehara Memorial Foundation research fellowship
- F.M. Kirby Foundation postdoctoral fellowship
- MINECO [SAF2012-31881]
- Fundacio Marato TV3 [464/C/2012]
- Spanish Ministry of Economy and Competitiveness (International Cooperation on Stem Cell Research Plan E) [PLE 2009/0100, SAF2012-39834]
- G. Harold and Leila Y. Mathers Charitable Foundation
- California Institute of Regenerative Medicine
- Ellison Medical Foundation
- National Institutes of Health [5U01HL107442]
- Leona M. and Harry B. Helmsley Charitable Trust [2012-PG-MED002]
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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.
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