|
Status |
Public on Dec 31, 2018 |
Title |
Modeling CADASIL vascular pathologies with patient-derived induced pluripotent stem cells |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
|
Summary |
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary cerebrovascular disease caused by a NOTCH3 mutation. However, the underlying cellular and molecular mechanisms remain unidentified. Here, we generated non-integrative induced pluripotent stem cells (iPSCs) from fibroblasts from a CADASIL patient harboring a heterozygous NOTCH3 mutation (c.3226C>T, p.R1076C). Vascular smooth muscle cells (VSMCs) differentiated from CADASIL-specific iPSCs showed transcriptional changes and disease-associated cellular dysfunction, including activation of the NF-kB signaling pathway, cytoskeleton disorganization, and excessive cell proliferation. In comparison, these abnormalities were not observed in vascular endothelial cells (VECs) derived from the patient’s iPSCs. Importantly, the abnormal upregulation of NF-kB target genes in CADASIL VSMCs was diminished by a NOTCH pathway inhibitor, providing a potential therapeutic strategy for CADASIL. Overall, using this iPSC-based disease model, our study identified clues for studying the disease mechanisms of CADASIL and developing treatment strategies for this disease.
|
|
|
Overall design |
Transcriptomic analyses of WT and Cadasil specific vascular cells.
|
|
|
Contributor(s) |
Liu G |
Citation(s) |
30778920 |
Submission date |
Dec 30, 2018 |
Last update date |
Apr 01, 2019 |
Contact name |
Zunpeng Liu |
E-mail(s) |
zunpengliu@163.com
|
Phone |
+86 15510715055
|
Organization name |
State Key Laboratory of Stem Cell and Reproductive Biology
|
Department |
Institute of Zoology, Chinese Academy of Sciences
|
Lab |
Jing Qu
|
Street address |
Beichen West Road
|
City |
Beijing |
ZIP/Postal code |
100101 |
Country |
China |
|
|
Platforms (1) |
|
Samples (12)
|
|
Relations |
BioProject |
PRJNA512232 |
SRA |
SRP174896 |