JOM KITA KE POLITEKNIK

Cooperative ETS Transcription Factors Enforce Adult Endothelial Cell Fate and Cardiovascular Homeostasis (Record no. 2174)

MARC details
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Personal name Gomez-Salinero, Jesus M
Relator term author
9 (RLIN) 2545
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Title Cooperative ETS Transcription Factors Enforce Adult Endothelial Cell Fate and Cardiovascular Homeostasis
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Date of publication, distribution, etc. 2022-10.
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General note /pmc/articles/PMC7614113/
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General note /pubmed/36713285
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Summary, etc. Current 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.
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Language note en
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Topical term or geographic name as entry element Article
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Genre/form data or focus term Text
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Personal name Itkin, Tomer
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9 (RLIN) 2546
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Houghton, Sean
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9 (RLIN) 2547
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Badwe, Chaitanya
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9 (RLIN) 2548
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Personal name Lin, Yang
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9 (RLIN) 2549
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Personal name Kalna, Viktoria
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9 (RLIN) 2550
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Personal name Dufton, Neil
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9 (RLIN) 2551
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Personal name Peghaire, Claire R
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9 (RLIN) 2552
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Yokoyama, Masataka
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9 (RLIN) 2553
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Wingo, Matthew
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9 (RLIN) 2554
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Lu, Tyler M.
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9 (RLIN) 2555
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Li, Ge
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9 (RLIN) 2556
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Personal name Xiang, Jenny Zhaoying
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9 (RLIN) 2557
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Personal name Hsu, Yen-Michael Sheng
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9 (RLIN) 2558
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Personal name Redmond, David
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9 (RLIN) 2559
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Personal name Schreiner, Ryan
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9 (RLIN) 2560
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Personal name Birdsey, Graeme M
Relator term author
9 (RLIN) 2561
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Personal name Randi, Anna M
Relator term author
9 (RLIN) 2562
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Personal name Rafii, Shahin
Relator term author
9 (RLIN) 2563
786 0# - DATA SOURCE ENTRY
Note Nat Cardiovasc Res
856 41 - ELECTRONIC LOCATION AND ACCESS
Uniform Resource Identifier <a href="http://dx.doi.org/10.1038/s44161-022-00128-3">http://dx.doi.org/10.1038/s44161-022-00128-3</a>
Public note Connect to this object online.

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