Title | Sox17 drives functional engraftment of endothelium converted from non-vascular cells. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Schachterle W, Badwe CR, Palikuqi B, Kunar B, Ginsberg M, Lis R, Yokoyama M, Elemento O, Scandura JM, Rafii S |
Journal | Nat Commun |
Volume | 8 |
Pagination | 13963 |
Date Published | 2017 Jan 16 |
ISSN | 2041-1723 |
Keywords | Amnion, 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 | <p>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.</p> |
DOI | 10.1038/ncomms13963 |
Alternate Journal | Nat Commun |
PubMed ID | 28091527 |
PubMed Central ID | PMC5260855 |
Grant List | R01 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 |