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Series GSE111908 Query DataSets for GSE111908
Status Public on May 03, 2018
Title Pluripotent stem cell model of Nakajo-Nishimura syndrome untangles proinflammatory pathways mediated by oxidative stress
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Nakajo-Nishimura syndrome (NNS) is an immunoproteasome-associated autoinflammatory disorder caused by a mutation of the PSMB8 gene. Although dysfunction of the immunoproteasome causes various cellular stresses attributed to the overproduction of inflammatory cytokines and chemokines in NNS, the underlying mechanisms of the autoinflammation are still largely unknown. To investigate and understand the mechanisms and signal pathways in NNS, we established a panel of isogenic pluripotent stem cell (PSC) lines with PSMB8 mutation. Activity of the immunoproteasome in PSMB8-mutant PSC-derived myeloid cell lines (MT-MLs) was reduced even without stimulation compared to non-mutant-MLs. Additionally, MT-MLs showed an overproduction of inflammatory cytokines and chemokines, with elevated reactive oxygen species (ROS) and phosphorylated p38 MAPK levels. Treatment with p38 MAPK inhibitor and anti-oxidants decreased the abnormal production of cytokines and chemokines. The current PSC model revealed a specific ROS-mediated inflammatory pathway, providing a platform for the discovery of alternative therapeutic options for NNS and related immunoproteasome disorders.
Overall design RNA-sequencing was conducted to identify the genes expressed in reponse to stimulation in different manners between WT and MT cells
Contributor(s) Honda-Ozaki F, Terashima M, Niwa A, Saito M
Citation(s) 29731430
Submission date Mar 15, 2018
Last update date May 17, 2019
Contact name Akira Niwa
Organization name CiRA, Kyoto University
Department Department of Clinical Application
Street address 53, Shogoin-Kawahara-cho, Sakyo-ku
City Kyoto
ZIP/Postal code 6068306
Country Japan
Platforms (1)
GPL18460 Illumina HiSeq 1500 (Homo sapiens)
Samples (8)
GSM3044855 RNA-seq_Ct-87-18-IplusT
GSM3044856 RNA-seq_Ct-87-18-Ut
GSM3044857 RNA-seq_Kh-1-KI-IplusT
BioProject PRJNA438520
SRA SRP135811

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE111908_RAW.tar 10.1 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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