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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Shichita, Takashi Yasukawa, Hideo Suzuki, Mayu Kasahara, Hidenori Kimura, Akihiro Sekiya, Takashi Yoshimura, Akihiko Shimizu, Nana Sasaki, Ken-ichiro Morita, Rimpei |
| Description | Author Affiliation: Morita R ( Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan); Suzuki M ( Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan); Kasahara H ( Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan); Shimizu N ( Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan); Shichita T ( Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan); Sekiya T ( Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan); Kimura A ( Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan); Sasaki K ( Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan.); Yasukawa H ( Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan.); Yoshimura A ( Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan); |
| Abstract | Transplantation of endothelial cells (ECs) is a promising therapeutic approach for ischemic disorders. In addition, the generation of ECs has become increasingly important for providing vascular plexus to regenerated organs, such as the liver. Although many attempts have been made to generate ECs from pluripotent stem cells and nonvascular cells, the minimum number of transcription factors that specialize in directly inducing vascular ECs remains undefined. Here, by screening 18 transcription factors that are important for both endothelial and hematopoietic development, we demonstrate that ets variant 2 (ETV2) alone directly converts primary human adult skin fibroblasts into functional vascular endothelial cells (ETVECs). In coordination with endogenous FOXC2 in fibroblasts, transduced ETV2 elicits expression of multiple key endothelial development factors, including FLI1, ERG, and TAL1, and induces expression of endothelial functional molecules, including EGFL7 and von Willebrand factor. Consequently, ETVECs exhibits EC characteristics in vitro and forms mature functional vasculature in Matrigel plugs transplanted in NOD SCID mice. Furthermore, ETVECs significantly improve blood flow recovery in a hind limb ischemic model using BALB/c-nu mice. Our study indicates that the creation of ETVECs provides further understanding of human EC development induced by ETV2. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 1 |
| Volume Number | 112 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2015-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Endothelial Cells Cytology Metabolism Fibroblasts Transcription Factors Animals Blood Vessels Cell Proliferation Forkhead Transcription Factors Mice, Inbred NOD Mice, SCID Perfusion Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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