TY - JOUR
T1 - Transcription factors ETS2 and MESP1 transdifferentiate human dermal fibroblasts into cardiac progenitors
AU - Islas, Jose Francisco
AU - Liu, Yu
AU - Weng, Kuo Chan
AU - Robertson, Matthew J.
AU - Zhang, Shuxing
AU - Prejusa, Allan
AU - Harger, John
AU - Tikhomirova, Dariya
AU - Chopra, Mani
AU - Iyer, Dinakar
AU - Mercola, Mark
AU - Oshima, Robert G.
AU - Willerson, James T.
AU - Potaman, Vladimir N.
AU - Schwartz, Robert J.
PY - 2012/8/7
Y1 - 2012/8/7
N2 - Unique insights for the reprograming of cell lineages have come from embryonic development in the ascidian Ciona, which is dependent upon the transcription factors Ci-ets1/2 and Ci-mesp to generate cardiac progenitors. We tested the idea that mammalian v-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) and mesoderm posterior (MESP) homolog may be used to convert human dermal fibroblasts into cardiac progenitors. Here we show that murine ETS2 has a critical role in directing cardiac progenitors during cardiopoiesis in embryonic stem cells. We then use lentivirus-mediated forced expression of human ETS2 to convert normal human dermal fibroblasts into replicative cells expressing the cardiac mesoderm marker KDR+. However, although neither ETS2 nor the purported cardiac master regulator MESP1 can by themselves generate cardiac progenitors de novo from fibroblasts, forced coexpression of ETS2 and MESP1 or cell treatment with purified proteins reprograms fibroblasts into cardiac progenitors, as shown by the de novo appearance of core cardiac transcription factors, Ca2+ transients, and sarcomeres. Our data indicate that ETS2 and MESP1 play important roles in a genetic network that governs cardiopoiesis.
AB - Unique insights for the reprograming of cell lineages have come from embryonic development in the ascidian Ciona, which is dependent upon the transcription factors Ci-ets1/2 and Ci-mesp to generate cardiac progenitors. We tested the idea that mammalian v-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) and mesoderm posterior (MESP) homolog may be used to convert human dermal fibroblasts into cardiac progenitors. Here we show that murine ETS2 has a critical role in directing cardiac progenitors during cardiopoiesis in embryonic stem cells. We then use lentivirus-mediated forced expression of human ETS2 to convert normal human dermal fibroblasts into replicative cells expressing the cardiac mesoderm marker KDR+. However, although neither ETS2 nor the purported cardiac master regulator MESP1 can by themselves generate cardiac progenitors de novo from fibroblasts, forced coexpression of ETS2 and MESP1 or cell treatment with purified proteins reprograms fibroblasts into cardiac progenitors, as shown by the de novo appearance of core cardiac transcription factors, Ca2+ transients, and sarcomeres. Our data indicate that ETS2 and MESP1 play important roles in a genetic network that governs cardiopoiesis.
KW - Cardiogenesis
KW - Fibroblast reprograming
KW - Kinetic imaging
KW - Protein transduction
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U2 - 10.1073/pnas.1120299109
DO - 10.1073/pnas.1120299109
M3 - Article
C2 - 22826236
AN - SCOPUS:84864696029
SN - 0027-8424
VL - 109
SP - 13016
EP - 13021
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 32
ER -