title: Transcription factors ETS2 and MESP1 transdifferentiate human dermal fibroblasts into cardiac progenitors.
abstract: 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.
authors: Graduate School of Biomedical Sciences, Institute of Bioscience and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA.
authors: Jose Francisco
authors: JF
authors: Islas
authors: Yu
authors: Y
authors: Liu
authors: Kuo-Chan
authors: KC
authors: Weng
authors: Matthew J
authors: MJ
authors: Robertson
authors: Shuxing
authors: S
authors: Zhang
authors: Allan
authors: A
authors: Prejusa
authors: John
authors: J
authors: Harger
authors: Dariya
authors: D
authors: Tikhomirova
authors: Mani
authors: M
authors: Chopra
authors: Dinakar
authors: D
authors: Iyer
authors: Mark
authors: M
authors: Mercola
authors: Robert G
authors: RG
authors: Oshima
authors: James T
authors: JT
authors: Willerson
authors: Vladimir N
authors: VN
authors: Potaman
authors: Robert J
authors: RJ
authors: Schwartz
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D054338:Cell Transdifferentiation / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D055786:Gene Knockout Techniques; D006801:Humans; D051379:Mice; D032386:Myoblasts, Cardiac / Q000166:cytology* / Q000502:physiology; D016133:Polymerase Chain Reaction; D050787:Proto-Oncogene Protein c-ets-2 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000166:cytology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D050787:Proto-Oncogene Protein c-ets-2; C494069:ETS2 protein, human; C494070:Ets2 protein, mouse; C101538:Mesp1 protein, mouse