Transcription factors ETS2 and MESP1 transdifferentiate human dermal fibroblasts into cardiac progenitors

Islas J.F.; Liu Y.; Weng K.-C.Robertson M.J.Zhang S.Prejusa A.Harger J.Tikhomirova D.Chopra M.Iyer D.Mercola M.Oshima R.G.Willerson J.T.Potaman V.N.Schwartz R.J.

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Transcription factors ETS2 and MESP1 transdifferentiate human dermal fibroblasts into cardiac progenitors

机译：Transcription factors ETS2 and MESP1 transdifferentiate human dermal fibroblasts into cardiac progenitors

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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, Ca~(2+) transients, and sarcomeres. Our data indicate that ETS2 and MESP1 play important roles in a genetic network that governs cardiopoiesis.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2012年第32期|13016-13021|共6页
作者
Islas J.F.; Liu Y.; Weng K.-C.Robertson M.J.Zhang S.Prejusa A.Harger J.Tikhomirova D.Chopra M.Iyer D.Mercola M.Oshima R.G.Willerson J.T.Potaman V.N.Schwartz R.J.;
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作者单位

Graduate School of Biomedical Sciences, Institute of Bioscience and Technology, Texas A and M Health Science Center, Houston, TX 77030, United States;

Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, United States;

Stem Cell Engineering Laboratory, Texas Heart Institute, St. Luke's Episcopal Hospital, Houston, TX 77030, United StatesDepartment of Medicine, Baylor College of Medicine, Houston, TX 77030, United StatesSanford-Burnham Medical Research Institute, San Diego, CA 92037, United States;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Cardiogenesis; Fibroblast reprograming; Kinetic imaging; Protein transduction;

Transcription factors ETS2 and MESP1 transdifferentiate human dermal fibroblasts into cardiac progenitors

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