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GSE25496
Homo sapiens
2 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Nasu-Hakola disease (NHD), also designated polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL; OMIM 221770), is a rare autosomal recessive disorder, characterized by progressive presenile dementia and formation of multifocal bone cysts, caused by genetic mutations of DAP12 and TREM2, which constitute a receptor/adapter signaling complex expressed on osteoclasts, dendritic cells, macrophages, and microglia. No Japanese patients with TREM2 mutations have been reported previously. We reported three siblings affected with NHD in a Japanese family. Among them, two died of NHD during the fourth decade of life. The transcriptome was studied in the autopsized brain of one patient. We found a homozygous conversion of a single nucleotide T to C at the second position of intron 3 in the splice-donor consensus site (c.482+2T>C) of the TREM2 gene, resulting in exon 3 skipping. We identified 136 upregulated genes involved in inflammatory response and immune cell trafficking and 188 downregulated genes including a battery of GABA receptor subunits and synaptic proteins in the patients brain.
Publication Title
Nasu-Hakola disease with a splicing mutation of TREM2 in a Japanese family.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Rattus norvegicus
- 4 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Pax6 is one of the important transcription factors involved in regional specification and neurogenesis in the developing cortex.
Publication Title
Dmrta1 regulates proneural gene expression downstream of Pax6 in the mammalian telencephalon.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of MMP1 as a novel risk factor for intracranial aneurysms in ADPKD using iPSC models.
Sample Metadata Fields
Sex, Specimen part, Disease stage, Subject
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
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.
Publication Title
Identification of MMP1 as a novel risk factor for intracranial aneurysms in ADPKD using iPSC models.
Sample Metadata Fields
Sex, Specimen part, Disease stage, Subject
View Samples