Abstract：
:Direct reprogramming of adult somatic cells into alternative cell types has been shown for several lineages. We previously showed that GATA4, MEF2C, and TBX5 (GMT) directly reprogrammed nonmyocyte mouse heart cells into induced cardiomyocyte-like cells (iCMs) in vitro and in vivo. However, GMT alone appears insufficient in human fibroblasts, at least in vitro. Here, we show that GMT plus ESRRG and MESP1 induced global cardiac gene-expression and phenotypic shifts in human fibroblasts derived from embryonic stem cells, fetal heart, and neonatal skin. Adding Myocardin and ZFPM2 enhanced reprogramming, including sarcomere formation, calcium transients, and action potentials, although the efficiency remained low. Human iCM reprogramming was epigenetically stable. Furthermore, we found that transforming growth factor β signaling was important for, and improved the efficiency of, human iCM reprogramming. These findings demonstrate that human fibroblasts can be directly reprogrammed toward the cardiac lineage, and lay the foundation for future refinements in vitro and in vivo.
journal_name
Stem Cell Reportsjournal_title
Stem cell reportsauthors
Fu JD,Stone NR,Liu L,Spencer CI,Qian L,Hayashi Y,Delgado-Olguin P,Ding S,Bruneau BG,Srivastava Ddoi
10.1016/j.stemcr.2013.07.005subject
Has Abstractpub_date
2013-08-22 00:00:00pages
235-47issue
3issn
2213-6711pii
S2213-6711(13)00054-4journal_volume
1pub_type
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