Modeling Fanconi anemia pathogenesis and therapeutics using integration-free patient iPSCs
Liu, Guang-Hui (Salk Institute for Biological Studies (La Jolla, Estats Units d'Amèrica). Laboratory of Gene Expression)
Suzuki, Keiichiro (Salk Institute for Biological Studies (La Jolla, Estats Units d'Amèrica). Laboratory of Gene Expression)
Li, Mo (Salk Institute for Biological Studies (La Jolla, Estats Units d'Amèrica). Laboratory of Gene Expression)
Qu, Jing (Salk Institute for Biological Studies (La Jolla, Estats Units d'Amèrica). Laboratory of Gene Expression)
Montserrat, Núria (Centro de Medicina Regenerativa de Barcelona)
Tarantino, Carolina (Centro de Medicina Regenerativa de Barcelona)
Gu, Ying (Salk Institute for Biological Studies (La Jolla, Estats Units d'Amèrica). Laboratory of Gene Expression)
Yi, Fei (Salk Institute for Biological Studies (La Jolla, Estats Units d'Amèrica). Laboratory of Gene Expression)
Xu, Xiuling (Zhongguo ke xue yuan. National Laboratory of Biomacromolecules)
Zhang, Weiqi (Zhongguo ke xue yuan. National Laboratory of Biomacromolecules)
Ruiz, Sergio (Salk Institute for Biological Studies (La Jolla, Estats Units d'Amèrica). Laboratory of Gene Expression)
Plongthongkum, Nongluk (University of California. Department of Bioengineering)
Zhang, Kun (University of California. Department of Bioengineering)
Masuda, Shigeo (Salk Institute for Biological Studies (La Jolla, Estats Units d'Amèrica). Laboratory of Gene Expression)
Nivet, Emmanuel (Salk Institute for Biological Studies (La Jolla, Estats Units d'Amèrica). Laboratory of Gene Expression)
Tsunokawa, Yuji (Salk Institute for Biological Studies (La Jolla, Estats Units d'Amèrica). Laboratory of Gene Expression)
Soligalla, Rupa Devi (Salk Institute for Biological Studies (La Jolla, Estats Units d'Amèrica). Laboratory of Gene Expression)
Goebl, April (Salk Institute for Biological Studies (La Jolla, Estats Units d'Amèrica). Laboratory of Gene Expression)
Aizawa, Emi (Salk Institute for Biological Studies (La Jolla, Estats Units d'Amèrica). Laboratory of Gene Expression)
Kim, Na Young (Salk Institute for Biological Studies (La Jolla, Estats Units d'Amèrica). Laboratory of Gene Expression)
Kim, Jessica (Salk Institute for Biological Studies (La Jolla, Estats Units d'Amèrica). Laboratory of Gene Expression)
Dubova, Ilir (Salk Institute for Biological Studies (La Jolla, Estats Units d'Amèrica). Laboratory of Gene Expression)
Li, Ying (Zhongguo ke xue yuan. National Laboratory of Biomacromolecules)
Ren, Ruotong (Zhongguo ke xue yuan. National Laboratory of Biomacromolecules)
Benner, Chris (Salk Institute for Biological Studies (La Jolla, Estats Units d'Amèrica))
Sol, Antonio del (Luxembourg Centre for Systems Biomedicine)
Bueren, Juan (Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz)
Trujillo Quintero, Juan Pablo (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Surrallés i Calonge, Jordi (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Cappelli, Enrico (Istituto "Giannina Gaslini" di Genova)
Dufour, Carlo (Istituto "Giannina Gaslini" di Genova)
Rodriguez Esteban, Concepción (Salk Institute for Biological Studies (La Jolla, Estats Units d'Amèrica). Laboratory of Gene Expression)
Izpisúa Belmonte, Juan Carlos (Salk Institute for Biological Studies (La Jolla, Estats Units d'Amèrica). Laboratory of Gene Expression)

Data:	2014
Resum:	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.
Resum:	Altres ajuts: Strategic Priority Research Program of the Chinese Academy of Sciences (XDA01020312), National Basic Research Program of China (973 Program,2014CB964600;2014CB910500), NSFC (81271266, 31222039, 81330008, 31201111, 81371342, 81300261, 81300677), Key Research Program of the Chinese Academy of Sciences (KJZD-EW-TZ-L05), Beijing Natural Science Foundation (7141005; 5142016), the Thousand Young Talents program of China, National Laboratory of Biomacromolecules (012kf02, 2013kf05;2013kf11;2014kf02), and State Key Laboratory of Drug Research (SIMM1302KF-17). M. L. and K. S. are supported by CIRM fellowship. N. M was partially supported by La Fundació Privada La Marató de TV3, 121430/31/32. Y. T. was partially supported by an Uehara Memorial Foundation research fellowship. E. N. was partially supported by an F. M. Kirby Foundation postdoctoral fellowship. J. S. was supported by Fundació Marató TV3 (464/C/2012). J. A. B. was supported by grants from La Fundació Privada La Marató de TV3, 121430/31/32. J. C. I. B. was supported by grants from the G. Harold and Leila Y. Mathers Charitable Foundation, The California Institute of Regenerative Medicine, Ellison Medical Foundation, and The Leona M. and Harry B. Helmsley Charitable Trust grant #2012-PG-MED002.
Ajuts:	Ministerio de Economía y Competitividad PLE 2009-0164 Ministerio de Economía y Competitividad SAF2012-31881 Ministerio de Economía y Competitividad PLE 2009/0100 Ministerio de Economía y Competitividad SAF2012-39834
Drets:	Tots els drets reservats.
Llengua:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Matèria:	Fanconi anemia
Publicat a:	Nature communications, Vol. 5, article 4330 (July 2014) , ISSN 2041-1723

DOI: 10.1038/ncomms5330
PMID: 24999918

Post-print 35 p, 2.1 MB

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