New Protocol to Optimize iPS Cells for Genome Analysis of Fibrodysplasia Ossificans Progressiva.
Stem Cells
; 33(6): 1730-42, 2015 Jun.
Article
in En
| MEDLINE
| ID: mdl-25773749
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteogenesis
/
Genome, Human
/
Cell Differentiation
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Chondrogenesis
/
Induced Pluripotent Stem Cells
/
Myositis Ossificans
Limits:
Humans
Language:
En
Journal:
Stem Cells
Year:
2015
Document type:
Article
Affiliation country: