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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-12

AUTHORS

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

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. More... »

PAGES

4330

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms5330

    DOI

    http://dx.doi.org/10.1038/ncomms5330

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1049608507

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/24999918


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