| 000 | 02713 am a22004093u 4500 | ||
|---|---|---|---|
| 042 | _adc | ||
| 100 | 1 | 0 |
_aGomez-Salinero, Jesus M _eauthor _92545 |
| 700 | 1 | 0 |
_aItkin, Tomer _eauthor _92546 |
| 700 | 1 | 0 |
_aHoughton, Sean _eauthor _92547 |
| 700 | 1 | 0 |
_aBadwe, Chaitanya _eauthor _92548 |
| 700 | 1 | 0 |
_aLin, Yang _eauthor _92549 |
| 700 | 1 | 0 |
_aKalna, Viktoria _eauthor _92550 |
| 700 | 1 | 0 |
_aDufton, Neil _eauthor _92551 |
| 700 | 1 | 0 |
_aPeghaire, Claire R _eauthor _92552 |
| 700 | 1 | 0 |
_aYokoyama, Masataka _eauthor _92553 |
| 700 | 1 | 0 |
_aWingo, Matthew _eauthor _92554 |
| 700 | 1 | 0 |
_aLu, Tyler M. _eauthor _92555 |
| 700 | 1 | 0 |
_aLi, Ge _eauthor _92556 |
| 700 | 1 | 0 |
_aXiang, Jenny Zhaoying _eauthor _92557 |
| 700 | 1 | 0 |
_aHsu, Yen-Michael Sheng _eauthor _92558 |
| 700 | 1 | 0 |
_aRedmond, David _eauthor _92559 |
| 700 | 1 | 0 |
_aSchreiner, Ryan _eauthor _92560 |
| 700 | 1 | 0 |
_aBirdsey, Graeme M _eauthor _92561 |
| 700 | 1 | 0 |
_aRandi, Anna M _eauthor _92562 |
| 700 | 1 | 0 |
_aRafii, Shahin _eauthor _92563 |
| 245 | 0 | 0 | _aCooperative ETS Transcription Factors Enforce Adult Endothelial Cell Fate and Cardiovascular Homeostasis |
| 260 | _c2022-10. | ||
| 500 | _a/pmc/articles/PMC7614113/ | ||
| 500 | _a/pubmed/36713285 | ||
| 520 | _aCurrent dogma dictates that during adulthood, endothelial cells (ECs) are locked in an immutable stable homeostatic state. By contrast, herein we show that maintenance of EC fate and function are linked and active processes, which depend on the constitutive cooperativity of only two ETS-transcription factors (TFs) ERG and Fli1. While deletion of either Fli1 or ERG manifest subtle vascular dysfunction, their combined genetic deletion in adult EC results in acute vasculopathy and multiorgan failure, due to loss of EC fate and integrity, hyperinflammation, and spontaneous thrombosis, leading to death. ERG and Fli1 co-deficiency cause rapid transcriptional silencing of pan- and organotypic vascular core genes, with dysregulation of inflammation and coagulation pathways. Vascular hyperinflammation leads to impaired hematopoiesis with myeloid skewing. Accordingly, enforced ERG and FLI1 expression in adult human mesenchymal stromal cells activates vascular programs and functionality enabling engraftment of perfusable vascular network. GWAS-analysis identified vascular diseases are associated with FLI1/Erg mutations. Constitutive expression of ERG and Fli1 uphold EC fate, physiological function, and resilience in adult vasculature; while their functional loss can contribute to systemic human diseases. | ||
| 540 | _a | ||
| 546 | _aen | ||
| 690 | _aArticle | ||
| 655 | 7 |
_aText _2local |
|
| 786 | 0 | _nNat Cardiovasc Res | |
| 856 | 4 | 1 |
_uhttp://dx.doi.org/10.1038/s44161-022-00128-3 _zConnect to this object online. |
| 999 |
_c2011 _d2011 |
||