ArticleCirculation research2017
Direct Reprogramming of Human Dermal Fibroblasts Into Endothelial Cells Using ER71/ETV2.
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Article in Circulation research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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96citing papers in PubMed
5.0field-weighted citation impact, top 4% of its field
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Who cites it
96 citing papers in PubMed, 138 citations in OpenAlex.
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36 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 4 institutions in 2 countries.
Sangho LeeFrom the Department of Pharmacology, College of Medicine, University of Illinois at Chicago (C.P., E.J.K.); Department of Pediatrics, Children's Heart Research and Outcomes Center, Emory University School of Medicine, Atlanta, GA (C.P., J.Y.K., S.Y.O.); Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (S.L., J.W.H., K.C., S.K., H.J.A., C.M.S., S.S., Y.-s.Y.); Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT (Y.T., I.-H.P.); and Division of Cardiology, Department of Medicine, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea (S.-J.L., Y.-s.Y.).
Changwon ParkFrom the Department of Pharmacology, College of Medicine, University of Illinois at Chicago (C.P., E.J.K.); Department of Pediatrics, Children's Heart Research and Outcomes Center, Emory University School of Medicine, Atlanta, GA (C.P., J.Y.K., S.Y.O.); Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (S.L., J.W.H., K.C., S.K., H.J.A., C.M.S., S.S., Y.-s.Y.); Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT (Y.T., I.-H.P.); and Division of Cardiology, Department of Medicine, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea (S.-J.L., Y.-s.Y.).
Ji Woong HanFrom the Department of Pharmacology, College of Medicine, University of Illinois at Chicago (C.P., E.J.K.); Department of Pediatrics, Children's Heart Research and Outcomes Center, Emory University School of Medicine, Atlanta, GA (C.P., J.Y.K., S.Y.O.); Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (S.L., J.W.H., K.C., S.K., H.J.A., C.M.S., S.S., Y.-s.Y.); Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT (Y.T., I.-H.P.); and Division of Cardiology, Department of Medicine, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea (S.-J.L., Y.-s.Y.).
Ju Young KimFrom the Department of Pharmacology, College of Medicine, University of Illinois at Chicago (C.P., E.J.K.); Department of Pediatrics, Children's Heart Research and Outcomes Center, Emory University School of Medicine, Atlanta, GA (C.P., J.Y.K., S.Y.O.); Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (S.L., J.W.H., K.C., S.K., H.J.A., C.M.S., S.S., Y.-s.Y.); Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT (Y.T., I.-H.P.); and Division of Cardiology, Department of Medicine, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea (S.-J.L., Y.-s.Y.).
Kyuwon ChoFrom the Department of Pharmacology, College of Medicine, University of Illinois at Chicago (C.P., E.J.K.); Department of Pediatrics, Children's Heart Research and Outcomes Center, Emory University School of Medicine, Atlanta, GA (C.P., J.Y.K., S.Y.O.); Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (S.L., J.W.H., K.C., S.K., H.J.A., C.M.S., S.S., Y.-s.Y.); Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT (Y.T., I.-H.P.); and Division of Cardiology, Department of Medicine, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea (S.-J.L., Y.-s.Y.).
Eun Jae KimFrom the Department of Pharmacology, College of Medicine, University of Illinois at Chicago (C.P., E.J.K.); Department of Pediatrics, Children's Heart Research and Outcomes Center, Emory University School of Medicine, Atlanta, GA (C.P., J.Y.K., S.Y.O.); Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (S.L., J.W.H., K.C., S.K., H.J.A., C.M.S., S.S., Y.-s.Y.); Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT (Y.T., I.-H.P.); and Division of Cardiology, Department of Medicine, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea (S.-J.L., Y.-s.Y.).
Sangsung KimFrom the Department of Pharmacology, College of Medicine, University of Illinois at Chicago (C.P., E.J.K.); Department of Pediatrics, Children's Heart Research and Outcomes Center, Emory University School of Medicine, Atlanta, GA (C.P., J.Y.K., S.Y.O.); Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (S.L., J.W.H., K.C., S.K., H.J.A., C.M.S., S.S., Y.-s.Y.); Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT (Y.T., I.-H.P.); and Division of Cardiology, Department of Medicine, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea (S.-J.L., Y.-s.Y.).
Shin-Jeong LeeFrom the Department of Pharmacology, College of Medicine, University of Illinois at Chicago (C.P., E.J.K.); Department of Pediatrics, Children's Heart Research and Outcomes Center, Emory University School of Medicine, Atlanta, GA (C.P., J.Y.K., S.Y.O.); Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (S.L., J.W.H., K.C., S.K., H.J.A., C.M.S., S.S., Y.-s.Y.); Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT (Y.T., I.-H.P.); and Division of Cardiology, Department of Medicine, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea (S.-J.L., Y.-s.Y.).
Se Yeong OhFrom the Department of Pharmacology, College of Medicine, University of Illinois at Chicago (C.P., E.J.K.); Department of Pediatrics, Children's Heart Research and Outcomes Center, Emory University School of Medicine, Atlanta, GA (C.P., J.Y.K., S.Y.O.); Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (S.L., J.W.H., K.C., S.K., H.J.A., C.M.S., S.S., Y.-s.Y.); Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT (Y.T., I.-H.P.); and Division of Cardiology, Department of Medicine, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea (S.-J.L., Y.-s.Y.).
Yoshiaki TanakaFrom the Department of Pharmacology, College of Medicine, University of Illinois at Chicago (C.P., E.J.K.); Department of Pediatrics, Children's Heart Research and Outcomes Center, Emory University School of Medicine, Atlanta, GA (C.P., J.Y.K., S.Y.O.); Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (S.L., J.W.H., K.C., S.K., H.J.A., C.M.S., S.S., Y.-s.Y.); Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT (Y.T., I.-H.P.); and Division of Cardiology, Department of Medicine, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea (S.-J.L., Y.-s.Y.).
In-Hyun ParkFrom the Department of Pharmacology, College of Medicine, University of Illinois at Chicago (C.P., E.J.K.); Department of Pediatrics, Children's Heart Research and Outcomes Center, Emory University School of Medicine, Atlanta, GA (C.P., J.Y.K., S.Y.O.); Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (S.L., J.W.H., K.C., S.K., H.J.A., C.M.S., S.S., Y.-s.Y.); Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT (Y.T., I.-H.P.); and Division of Cardiology, Department of Medicine, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea (S.-J.L., Y.-s.Y.).
Hyo Jae AnFrom the Department of Pharmacology, College of Medicine, University of Illinois at Chicago (C.P., E.J.K.); Department of Pediatrics, Children's Heart Research and Outcomes Center, Emory University School of Medicine, Atlanta, GA (C.P., J.Y.K., S.Y.O.); Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (S.L., J.W.H., K.C., S.K., H.J.A., C.M.S., S.S., Y.-s.Y.); Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT (Y.T., I.-H.P.); and Division of Cardiology, Department of Medicine, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea (S.-J.L., Y.-s.Y.).
Claire Min ShinFrom the Department of Pharmacology, College of Medicine, University of Illinois at Chicago (C.P., E.J.K.); Department of Pediatrics, Children's Heart Research and Outcomes Center, Emory University School of Medicine, Atlanta, GA (C.P., J.Y.K., S.Y.O.); Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (S.L., J.W.H., K.C., S.K., H.J.A., C.M.S., S.S., Y.-s.Y.); Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT (Y.T., I.-H.P.); and Division of Cardiology, Department of Medicine, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea (S.-J.L., Y.-s.Y.).
Shraya SharmaFrom the Department of Pharmacology, College of Medicine, University of Illinois at Chicago (C.P., E.J.K.); Department of Pediatrics, Children's Heart Research and Outcomes Center, Emory University School of Medicine, Atlanta, GA (C.P., J.Y.K., S.Y.O.); Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (S.L., J.W.H., K.C., S.K., H.J.A., C.M.S., S.S., Y.-s.Y.); Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT (Y.T., I.-H.P.); and Division of Cardiology, Department of Medicine, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea (S.-J.L., Y.-s.Y.).
Young-Sup YoonFrom the Department of Pharmacology, College of Medicine, University of Illinois at Chicago (C.P., E.J.K.); Department of Pediatrics, Children's Heart Research and Outcomes Center, Emory University School of Medicine, Atlanta, GA (C.P., J.Y.K., S.Y.O.); Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (S.L., J.W.H., K.C., S.K., H.J.A., C.M.S., S.S., Y.-s.Y.); Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT (Y.T., I.-H.P.); and Division of Cardiology, Department of Medicine, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea (S.-J.L., Y.-s.Y.) yyoon5@emory.edu cpark23@emory.edu.
Yale Cancer Center · USYonsei University · KREmory University · USUniversity of Illinois Chicago · US
Funding
Atlanta Clinical and Translational Science Institute (ACTSI) RenewalUL1TR000454 · NCATS · EMORY UNIVERSITY · PI STEPHENS, DAVID S · 2012 to 2016
$25.8MCell therapy for diabetic peripheral neurovascular complicationsDP3DK094346 · NIDDK · EMORY UNIVERSITY · PI CHENG, XIAODONG, YOON, YOUNG-SUP · 2011 to 2011
$6.1MMechanisms of ER71/ETV2-regulated VascularizationR01HL119291 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI PARK, CHANGWON · 2013 to 2022
$3.2MEffects of reprogrammed and engineered MSCs on diabetic complicationsDP3DK108245 · NIDDK · EMORY UNIVERSITY · PI YOON, YOUNG-SUP · 2015 to 2016
$2.6MStem Cell-based therapy for LymphedemaR01HL127759 · NHLBI · EMORY UNIVERSITY · PI YOON, YOUNG-SUP · 2015 to 2018
$1.6MCardiac Regeneration with Bioengineered Human Stem CellsR01HL129511 · NHLBI · EMORY UNIVERSITY · PI YOON, YOUNG-SUP · 2016 to 2019
$1.6MNCATS NIH HHS UL1 TR000454NHLBI NIH HHS R01 HL119291NHLBI NIH HHS R01 HL127759NHLBI NIH HHS R01 HL129511NIDDK NIH HHS DP3 DK094346NIDDK NIH HHS DP3 DK108245
Abstract
rationaleDirect conversion or reprogramming of human postnatal cells into endothelial cells (ECs), bypassing stem or progenitor cell status, is crucial for regenerative medicine, cell therapy, and pathophysiological investigation but has remained largely unexplored.
objectiveWe sought to directly reprogram human postnatal dermal fibroblasts to ECs with vasculogenic and endothelial transcription factors and determine their vascularizing and therapeutic potential. METHODS AND
resultsWe utilized various combinations of 7 EC transcription factors to transduce human postnatal dermal fibroblasts and found that ER71/ETV2 (ETS variant 2) alone best induced endothelial features. KDR
conclusionsThis study for the first time demonstrates that ER71/ETV2 alone can directly reprogram human postnatal cells to functional, mature ECs after an intervening transgene-free period. These rECs could be valuable for cell therapy, personalized disease investigation, and exploration of the reprogramming process.
Indexed as
AnimalsCell DifferentiationCells, CulturedCellular Reprogramming TechniquesEndothelial CellsFibroblastsHindlimbHumansHuman Umbilical Vein Endothelial CellsIschemiaMaleMiceMice, NudeNeovascularization, PhysiologicTranscription FactorsETV2 protein, humanTranscription Factorscell therapyendothelial cellsfibroblastsischemiaregenerative medicine
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