title: Sox17 drives functional engraftment of endothelium converted from non-vascular cells.
abstract: Transplanting vascular endothelial cells (ECs) to support metabolism and express regenerative paracrine factors is a strategy to treat vasculopathies and to promote tissue regeneration. However, transplantation strategies have been challenging to develop, because ECs are difficult to culture and little is known about how to direct them to stably integrate into vasculature. Here we show that only amniotic cells could convert to cells that maintain EC gene expression. Even so, these converted cells perform sub-optimally in transplantation studies. Constitutive Akt signalling increases expression of EC morphogenesis genes, including Sox17, shifts the genomic targeting of Fli1 to favour nearby Sox consensus sites and enhances the vascular function of converted cells. Enforced expression of Sox17 increases expression of morphogenesis genes and promotes integration of transplanted converted cells into injured vessels. Thus, Ets transcription factors specify non-vascular, amniotic cells to EC-like cells, whereas Sox17 expression is required to confer EC function.
authors.affiliation: Division of Regenerative Medicine, Department of Medicine, Ansary Stem Cell Institute, Weill Cornell Medicine, 1300 York Avenue, Room A-863, New York, New York 10065, USA.
authors.forename: William
authors.initials: W
authors.lastname: Schachterle
authors.affiliation: Division of Regenerative Medicine, Department of Medicine, Ansary Stem Cell Institute, Weill Cornell Medicine, 1300 York Avenue, Room A-863, New York, New York 10065, USA.
authors.forename: Chaitanya R
authors.initials: CR
authors.lastname: Badwe
authors.affiliation: Division of Regenerative Medicine, Department of Medicine, Ansary Stem Cell Institute, Weill Cornell Medicine, 1300 York Avenue, Room A-863, New York, New York 10065, USA.
authors.forename: Brisa
authors.initials: B
authors.lastname: Palikuqi
authors.affiliation: Division of Regenerative Medicine, Department of Medicine, Ansary Stem Cell Institute, Weill Cornell Medicine, 1300 York Avenue, Room A-863, New York, New York 10065, USA.
authors.forename: Balvir
authors.initials: B
authors.lastname: Kunar
authors.affiliation: Angiocrine Bioscience, New York, New York, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Ginsberg
authors.affiliation: Division of Regenerative Medicine, Department of Medicine, Ansary Stem Cell Institute, Weill Cornell Medicine, 1300 York Avenue, Room A-863, New York, New York 10065, USA.
authors.forename: Raphael
authors.initials: R
authors.lastname: Lis
authors.affiliation: Division of Regenerative Medicine, Department of Medicine, Ansary Stem Cell Institute, Weill Cornell Medicine, 1300 York Avenue, Room A-863, New York, New York 10065, USA.
authors.forename: Masataka
authors.initials: M
authors.lastname: Yokoyama
authors.affiliation: HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College, New York, New York 10065, USA.
authors.forename: Olivier
authors.initials: O
authors.lastname: Elemento
authors.affiliation: Division of Regenerative Medicine, Department of Medicine, Ansary Stem Cell Institute, Weill Cornell Medicine, 1300 York Avenue, Room A-863, New York, New York 10065, USA.|Department of Medicine, Hematology-Oncology, Weill Cornell Medical College and the New York Presbyterian Hospital, New York, New York 10065, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Scandura
authors.affiliation: Division of Regenerative Medicine, Department of Medicine, Ansary Stem Cell Institute, Weill Cornell Medicine, 1300 York Avenue, Room A-863, New York, New York 10065, USA.
authors.forename: Shahin
authors.initials: S
authors.lastname: Rafii
mesh_terms: D000650:Amnion / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D000818:Animals; D042783:Endothelial Cells / Q000378:metabolism / Q000637:transplantation*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051789:Proto-Oncogene Protein c-fli-1 / Q000235:genetics / Q000378:metabolism; D012038:Regeneration; D055760:SOXF Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014652:Vascular Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*
chemical_list: C497426:Fli1 protein, mouse; D051789:Proto-Oncogene Protein c-fli-1; D055760:SOXF Transcription Factors