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| Status |
Public on Jun 11, 2012 |
| Title |
Induced pluripotent stem cells from CINCA syndrome patients as a model for dissecting somatic mosaicism and drug discovery |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Chronic infantile neurological cutaneous and articular (CINCA) syndrome is an IL-1-driven autoinflammatory disorder caused mainly by NLRP3 mutations. The pathogenesis of CINCA syndrome patients who carry NLRP3 mutations as somatic mosaicism has not been precisely described because of the difficulty in separating individual cells based on the presence or absence of the mutation. Here, we report the generation of NLRP3-mutant and non-mutant induced pluripotent stem cell (iPSC) lines from two CINCA syndrome patients with somatic mosaicism, and describe their differentiation into macrophages (iPS-MPs). We found that mutant cells are predominantly responsible for the pathogenesis in these mosaic patients because only mutant iPS-MPs showed the disease relevant phenotype of abnormal IL-1β secretion. We also confirmed that the existing anti-inflammatory compounds inhibited the abnormal IL-1β secretion, indicating that mutant iPS-MPs are applicable for drug screening for CINCA syndrome and other NLRP3-related inflammatory conditions. Our results illustrate that patient-derived iPSCs are useful for dissecting somatic mosaicism, and that NLRP3-mutant iPSCs can provide a valuable platform for drug discovery for multiple NLRP3-related disorders.
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| Overall design |
To characterize iPS and differentiated cells, RNA expression profiles were evaluated by microarray analysis.We analyzed iPC cells and macrophage from healthy volunteers and CINCA syndrome patients. Human ES cella and fibroblasts were used as control.
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| Contributor(s) |
Tanaka T, Takahashi K, Yamane M, Tomida S, Nakamura S, Oshima K, Niwa A, Nishikomori R, Kambe N, Hara H, Mitsuyama M, Morone N, Heuser JE, Yamamoto T, Watanabe A, Matsubara A, Ogawa S, Asaka I, Heike T, Yamanaka S, Nakahata T, Saito MK |
| Citation(s) |
22723549 |
| Submission date |
Jun 10, 2012 |
| Last update date |
Nov 27, 2018 |
| Contact name |
Akira Watanabe |
| E-mail(s) |
a.watanabe@aw-lab.kyoto
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| Organization name |
Kyoto University
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| Department |
Medical Innovation Center
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| Street address |
Shogoin-Kawahara-cho 53, Sakyo-ku
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| City |
Kyoto |
| State/province |
Kyoto |
| ZIP/Postal code |
606-8507 |
| Country |
Japan |
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| Platforms (1) |
| GPL13607 |
Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Feature Number version) |
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| Samples (15)
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| Relations |
| BioProject |
PRJNA168293 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE38626_RAW.tar |
51.6 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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