Transcriptomics

Dataset Information

1

Identification of a novel risk factor for intracranial aneurysms in ADPKD using iPSC models [Agilent]


ABSTRACT: Cardiovascular complications are the leading cause of death in autosomal dominant polycystic kidney disease (ADPKD), and intracranial aneurysm (ICA) causing subarachnoid hemorrhage is among the most serious complications. The diagnostic and therapeutic strategies for ICAs in ADPKD have not been fully established. We here generated induced pluripotent stem cells (iPSCs) from seven ADPKD patients, including four with ICAs. The vascular cells differentiated from ADPKD-iPSCs showed altered Ca2+ entry and gene expression profiles compared with those from control-iPSCs. We found that the expression level of a metalloenzyme gene, matrix metalloproteinase (MMP) 1, was specifically elevated in the iPSC-derived endothelia from ADPKD patients with ICAs. Furthermore, we confirmed a statistically significant correlation between the serum MMP1 levels and the development of ICAs in 354 ADPKD patients, indicating that the serum MMP1 levels may be a novel risk factor and become more beneficial when combined with other risk factors. These results suggest that cellular disease models with ADPKD-specific iPSCs can be used to study the disease mechanisms and to identify novel disease-related molecules or risk factors. The gene expression profiles of vascular endothelia and smooth muscle cells derived from control- and ADPKD-iPSCs were analyzed. Seven control-iPSC derived endothelial cells (ECs), seven ADPKD-iPSC derived ECs, ten control-iPSC derived vascular smooth muscle cells (SMCs), and seven ADPKD-iPSC derived SMCs were analyzed.

ORGANISM(S): Homo sapiens  

SUBMITTER: Fumihiko Shiota   Masahiro Nakamura  Akira Watanabe  Kenji Osafune  Tomonaga Ameku  Fumiyo Kitaoka  Naoki Amano 

PROVIDER: E-GEOD-74451 | ArrayExpress | 2016-08-04

SECONDARY ACCESSION(S): GSE74451PRJNA300447

REPOSITORIES: GEO, ArrayExpress

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Publications


Cardiovascular complications are the leading cause of death in autosomal dominant polycystic kidney disease (ADPKD), and intracranial aneurysm (ICA) causing subarachnoid hemorrhage is among the most serious complications. The diagnostic and therapeutic strategies for ICAs in ADPKD have not been fully established. We here generated induced pluripotent stem cells (iPSCs) from seven ADPKD patients, including four with ICAs. The vascular cells differentiated from ADPKD-iPSCs showed altered Ca(2+) en  ...[more]

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