Imperial College London
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ProfessorAnnaRandi

Faculty of Medicine, National Heart & Lung Institute

Head of Section for Vascular Science
 
 
 
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Contact

 

a.randi Website

 
 
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Location

 

L-block, room 533Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Gomez-Salinero:2022:10.1038/s44161-022-00128-3,
author = {Gomez-Salinero, J and Itkin, T and Houghton, S and Badwe, C and Lin, Y and Kalna, V and Dufton, N and Peghaire, C and Yokoyama, M and Wingo, M and Lu, T and Li, G and Xiang, JZ and Hsu, Y-MS and Redmond, D and Schreiner, R and Birdsey, G and Randi, A and Rafii, S},
doi = {10.1038/s44161-022-00128-3},
journal = {Nature Cardiovascular Research},
pages = {882--899},
title = {Cooperative ETS transcription factors enforce adult endothelial cell fate and cardiovascular homeostasis.},
url = {http://dx.doi.org/10.1038/s44161-022-00128-3},
volume = {1},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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. Although deletion of either ERG or Fli1 manifests subtle vascular dysfunction, their combined genetic deletion in adult ECs results in acute vasculopathy and multi-organ failure, due to loss of EC fate and integrity, hyperinflammation and spontaneous thrombosis, leading to death. ERG and Fli1 co-deficiency causes 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 in vivo engraftment of a perfusable vascular network. Genome-wide association study analysis identified vascular diseases that are associated with FLI1/ERG mutations. Constitutive expression of ERG and Fli1 upholds EC fate, physiological function and resilience in adult vasculature, whereas their functional loss can contribute to systemic human diseases.
AU  - Gomez-Salinero,J
AU  - Itkin,T
AU  - Houghton,S
AU  - Badwe,C
AU  - Lin,Y
AU  - Kalna,V
AU  - Dufton,N
AU  - Peghaire,C
AU  - Yokoyama,M
AU  - Wingo,M
AU  - Lu,T
AU  - Li,G
AU  - Xiang,JZ
AU  - Hsu,Y-MS
AU  - Redmond,D
AU  - Schreiner,R
AU  - Birdsey,G
AU  - Randi,A
AU  - Rafii,S
DO  - 10.1038/s44161-022-00128-3
EP  - 899
PY  - 2022///
SN  - 2731-0590
SP  - 882
TI  - Cooperative ETS transcription factors enforce adult endothelial cell fate and cardiovascular homeostasis.
T2  - Nature Cardiovascular Research
UR  - http://dx.doi.org/10.1038/s44161-022-00128-3
UR  - https://www.nature.com/articles/s44161-022-00128-3
UR  - http://hdl.handle.net/10044/1/101140
VL  - 1
ER  -
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