Cooperative ETS transcription factors enforce adult endothelial cell fate and cardiovascular homeostasis

ETS转录因子家族 飞行1 生物 转录因子 细胞生物学 基因沉默 间充质干细胞 Erg公司 细胞命运测定 癌症研究 免疫学 内皮功能障碍 条件基因敲除 内皮干细胞 遗传学 表型 内分泌学 基因 神经科学 体外 视网膜
作者
Jesús M. Gómez-Salinero,Tomer Itkin,Sean Houghton,Chaitanya R. Badwe,Yang Lin,Viktoria Kalna,Neil Dufton,Claire Peghaire,Masataka Yokoyama,Matthew Wingo,Tyler M. Lu,Ge Li,Jenny Xiang,Yen‐Michael S. Hsu,David Redmond,Ryan Schreiner,Graeme M. Birdsey,Anna M. Randi,Shahin Rafii
出处
期刊:Nature Cardiovascular Research [Springer Nature]
卷期号:1 (10): 882-899 被引量:9
标识
DOI:10.1038/s44161-022-00128-3
摘要

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. Gomez-Salinero, Itkin et al. demonstrate the cooperative role of two ETS transcriptor factors, ERG and Fli1, in the active maintenance of endothelial cell homeostatic function. Loss of these two genes in adult mice leads to multi-organ failure, hyperinflammation, systemic thrombosis and death. In vitro, expression of both ERG and FLI1 induces human adult non-vascular mesenchymal stromal cells to acquire endothelial-like properties. In humans, several cardiovascular disorders and inflammatory-related diseases are linked to mutations in both genes.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
JamesPei应助宣兰采纳,获得10
刚刚
1秒前
1秒前
oookkay发布了新的文献求助10
2秒前
陈凝景完成签到,获得积分20
2秒前
咪咪虾条发布了新的文献求助10
2秒前
sff完成签到,获得积分10
3秒前
一二完成签到,获得积分10
3秒前
NexusExplorer应助keroro采纳,获得10
4秒前
清风徐来发布了新的文献求助10
4秒前
5秒前
5秒前
TAboo发布了新的文献求助10
5秒前
DJ发布了新的文献求助10
5秒前
orixero应助sorawing采纳,获得10
5秒前
顾矜应助DE2022采纳,获得10
6秒前
科研迪迦奥特曼完成签到,获得积分10
6秒前
6秒前
le000000发布了新的文献求助30
7秒前
秋雅发布了新的文献求助10
7秒前
我是老大应助逆旅采纳,获得10
7秒前
8秒前
8秒前
9秒前
9秒前
赘婿应助小米儿采纳,获得10
9秒前
hjh完成签到,获得积分20
9秒前
1028181661发布了新的文献求助10
10秒前
song给song的求助进行了留言
10秒前
AmyDong完成签到,获得积分10
11秒前
11秒前
清晨五点的沙滩完成签到,获得积分10
11秒前
星期八发布了新的文献求助10
12秒前
12秒前
sail发布了新的文献求助10
13秒前
Akim应助小鱼儿飞飞采纳,获得30
13秒前
keroro发布了新的文献求助10
14秒前
14秒前
万能图书馆应助hjh采纳,获得10
15秒前
15秒前
高分求助中
歯科矯正学 第7版(或第5版) 1004
Semiconductor Process Reliability in Practice 1000
Smart but Scattered: The Revolutionary Executive Skills Approach to Helping Kids Reach Their Potential (第二版) 1000
GROUP-THEORY AND POLARIZATION ALGEBRA 500
Mesopotamian divination texts : conversing with the gods : sources from the first millennium BCE 500
Days of Transition. The Parsi Death Rituals(2011) 500
The Heath Anthology of American Literature: Early Nineteenth Century 1800 - 1865 Vol. B 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3233445
求助须知:如何正确求助?哪些是违规求助? 2879969
关于积分的说明 8213423
捐赠科研通 2547415
什么是DOI,文献DOI怎么找? 1376927
科研通“疑难数据库(出版商)”最低求助积分说明 647713
邀请新用户注册赠送积分活动 623150