Abstract:
:Fibrodysplasia ossificans progressiva (FOP) patients carry a missense mutation in ACVR1 [617G > A (R206H)] that leads to hyperactivation of BMP-SMAD signaling. Contrary to a previous study, here we show that FOP fibroblasts showed an increased efficiency of induced pluripotent stem cell (iPSC) generation. This positive effect was attenuated by inhibitors of BMP-SMAD signaling (Dorsomorphin or LDN1931890) or transducing inhibitory SMADs (SMAD6 or SMAD7). In normal fibroblasts, the efficiency of iPSC generation was enhanced by transducing mutant ACVR1 (617G > A) or SMAD1 or adding BMP4 protein at early times during the reprogramming. In contrast, adding BMP4 at later times decreased iPSC generation. ID genes, transcriptional targets of BMP-SMAD signaling, were critical for iPSC generation. The BMP-SMAD-ID signaling axis suppressed p16/INK4A-mediated cell senescence, a major barrier to reprogramming. These results using patient cells carrying the ACVR1 R206H mutation reveal how cellular signaling and gene expression change during the reprogramming processes.
journal_name
Proc Natl Acad Sci U S Aauthors
Hayashi Y,Hsiao EC,Sami S,Lancero M,Schlieve CR,Nguyen T,Yano K,Nagahashi A,Ikeya M,Matsumoto Y,Nishimura K,Fukuda A,Hisatake K,Tomoda K,Asaka I,Toguchida J,Conklin BR,Yamanaka Sdoi
10.1073/pnas.1603668113subject
Has Abstractpub_date
2016-11-15 00:00:00pages
13057-13062issue
46eissn
0027-8424issn
1091-6490pii
1603668113journal_volume
113pub_type
杂志文章abstract::We have isolated and analyzed a cDNA from the central nervous system of the mollusc Lymnaea stagnalis encoding a putative receptor, which might be a natural hybrid between two different classes of receptor proteins. Preceded by a signal peptide, two types of repeated sequences are present in the N-terminal part of the...
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