New Protocol to Optimize iPS Cells for Genome Analysis of Fibrodysplasia Ossificans Progressiva
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- Yoshihisa Matsumoto
- Department of Tissue Regeneration, Institute for Frontier Medical Sciences Kyoto University, Kyoto, Japan
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- Makoto Ikeya
- Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application Kyoto University, Kyoto, Japan
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- Kyosuke Hino
- Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application Kyoto University, Kyoto, Japan
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- Kazuhiko Horigome
- Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application Kyoto University, Kyoto, Japan
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- Makoto Fukuta
- Department of Tissue Regeneration, Institute for Frontier Medical Sciences Kyoto University, Kyoto, Japan
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- Makoto Watanabe
- Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application Kyoto University, Kyoto, Japan
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- Sanae Nagata
- Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application Kyoto University, Kyoto, Japan
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- Takuya Yamamoto
- Department of Reprogramming Science, Center for iPS Cell Research and Application Kyoto University, Kyoto, Japan
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- Takanobu Otsuka
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences Nagoya City University, Nagoya, Japan
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- Junya Toguchida
- Department of Tissue Regeneration, Institute for Frontier Medical Sciences Kyoto University, Kyoto, Japan
説明
<jats:title>Abstract</jats:title><jats:p>Successful in vitro disease-recapitulation using patient-specific induced pluripotent stem cells (iPSCs) requires two fundamental technical issues: appropriate control cells and robust differentiation protocols. To investigate fibrodysplasia ossificans progressiva (FOP), a rare genetic disease leading to extraskeletal bone formation through endochondral ossification, gene-corrected (rescued) iPSC clones (resFOP-iPSC) were generated from patient-derived iPSC (FOP-iPSC) as genetically matched controls, and the stepwise induction method of mesenchymal stromal cells (iMSCs) through neural crest cell (NCC) lineage was used to recapitulate the disease phenotype. FOP-iMSCs possessing enhanced chondrogenic ability were transcriptionally distinguishable from resFOP-iMSCs and activated the SMAD1/5/8 and SMAD2/3 pathways at steady state. Using this method, we identified MMP1 and PAI1 as genes responsible for accelerating the chondrogenesis of FOP-iMSCs. These data indicate that iMSCs through NCC lineage are useful for investigating the molecular mechanism of FOP and corresponding drug discovery. Stem Cells 2015;33:1730–1742</jats:p>
収録刊行物
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- Stem Cells
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Stem Cells 33 (6), 1730-1742, 2015-05-21
Oxford University Press (OUP)
