Sox17 drives functional engraftment of endothelium converted from non-vascular cells.

TitleSox17 drives functional engraftment of endothelium converted from non-vascular cells.
Publication TypeJournal Article
Year of Publication2017
AuthorsSchachterle W, Badwe CR, Palikuqi B, Kunar B, Ginsberg M, Lis R, Yokoyama M, Elemento O, Scandura JM, Rafii S
JournalNat Commun
Volume8
Pagination13963
Date Published2017 01 16
ISSN2041-1723
KeywordsAmnion, Animals, Endothelial Cells, Endothelium, Vascular, Female, Humans, Male, Mice, Mice, Inbred C57BL, Proto-Oncogene Protein c-fli-1, Regeneration, SOXF Transcription Factors, Vascular Diseases
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.

DOI10.1038/ncomms13963
Alternate JournalNat Commun
PubMed ID28091527
PubMed Central IDPMC5260855
Grant ListR01 HL115128 / HL / NHLBI NIH HHS / United States
M01 RR000047 / RR / NCRR NIH HHS / United States
T32 HL094284 / HL / NHLBI NIH HHS / United States
R01 HL128158 / HL / NHLBI NIH HHS / United States
R01 DK095039 / DK / NIDDK NIH HHS / United States
T32 HD060600 / HD / NICHD NIH HHS / United States
R01 HL119872 / HL / NHLBI NIH HHS / United States