CRISPR/Cas9-mediated gene knockout reveals a guardian role of NF-κB/RelA in maintaining the homeostasis of human vascular cells.
10.1007/s13238-018-0560-5
- Author:
Ping WANG
1
;
Zunpeng LIU
2
;
Xiaoqian ZHANG
2
;
Jingyi LI
1
;
Liang SUN
3
;
Zhenyu JU
4
;
Jian LI
3
;
Piu CHAN
5
;
Guang-Hui LIU
6
;
Weiqi ZHANG
7
;
Moshi SONG
8
;
Jing QU
9
Author Information
1. National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
2. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
3. The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, 100730, China.
4. Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou, 510632, China.
5. National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China.
6. National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. ghliu@ibp.ac.cn.
7. National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. weiqizhang@aliyun.com.
8. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. songmoshi@ioz.ac.cn.
9. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. qujing@ioz.ac.cn.
- Publication Type:Journal Article
- Keywords:
Apoptosis;
Inflammation;
NF-κB;
RelA;
Stem cell
- MeSH:
Blood Vessels;
cytology;
metabolism;
CRISPR-Cas Systems;
Embryonic Stem Cells;
cytology;
Gene Knockout Techniques;
Homeostasis;
Humans;
NF-kappa B;
deficiency;
metabolism;
Transcription Factor RelA;
deficiency;
metabolism
- From:
Protein & Cell
2018;9(11):945-965
- CountryChina
- Language:English
-
Abstract:
Vascular cell functionality is critical to blood vessel homeostasis. Constitutive NF-κB activation in vascular cells results in chronic vascular inflammation, leading to various cardiovascular diseases. However, how NF-κB regulates human blood vessel homeostasis remains largely elusive. Here, using CRISPR/Cas9-mediated gene editing, we generated RelA knockout human embryonic stem cells (hESCs) and differentiated them into various vascular cell derivatives to study how NF-κB modulates human vascular cells under basal and inflammatory conditions. Multi-dimensional phenotypic assessments and transcriptomic analyses revealed that RelA deficiency affected vascular cells via modulating inflammation, survival, vasculogenesis, cell differentiation and extracellular matrix organization in a cell type-specific manner under basal condition, and that RelA protected vascular cells against apoptosis and modulated vascular inflammatory response upon tumor necrosis factor α (TNFα) stimulation. Lastly, further evaluation of gene expression patterns in IκBα knockout vascular cells demonstrated that IκBα acted largely independent of RelA signaling. Taken together, our data reveal a protective role of NF-κB/RelA in modulating human blood vessel homeostasis and map the human vascular transcriptomic landscapes for the discovery of novel therapeutic targets.
