We enriched for prostate cancer cells by the selection system used in human iPS purification. Gene expression signature-based chemical prediction enabled us to identify candidate drugs for reverting the EOS (early transposon promoter, OCT4 and SOX2 enhancer) signature with chemoresistance into a chemosensitive phenotype.
Identification of drug candidate against prostate cancer from the aspect of somatic cell reprogramming.
Specimen part, Cell line, Treatment
View SamplesBackgroundAcute coronary syndrome (ACS) is sometimes accompanied by accelerated coagulability, lipid metabolism, and inflammatory responses, which are not attributable to the cardiac events alone. We hypothesized that the liver plays a pivotal role in the pathophysiology of ACS. We simultaneously analyzed the gene expression profiles of the liver and heart during acute myocardial ischemia in mice.
Altered hepatic gene expression profiles associated with myocardial ischemia.
Sex, Specimen part
View SamplesThe expression of four transcription factors (OCT3/4, SOX2, KLF4, and c-MYC) can reprogram mouse as well as human somatic cells to induced pluripotent stem (iPS) cells. Expression of the c-MYC, also known as an oncogene, might induce carcinogenesis and thus, iPS cells produced with the use of c-MYC transduction cannot be used for human therapeutic applications. Furthermore, reprogramming efficiency was significantly reduced in the absence of c-MYC transduction. Here, we generated iPS cells from mesenchymal stromal cells (MSCs) derived from human third molars (wisdom teeth) by retroviral transduction of OCT3/4, SOX2, and KLF4 without c-MYC. Interestingly, clonally expanded MSCs, named 10F-15, could be used for iPS cell generation with 100-fold higher efficiency compared to that of other clonally expanded MSCs and human dermal fibroblasts. These iPS cells resembled human embryonic stem (ES) cells in many aspects, including morphology, ES markers expression, global gene expression, epigenetic states, and the ability to differentiate into the three germ layers in vitro and in vivo. Because human third molars are discarded as clinical waste, our data indicate that MSCs isolated from human third molars are a valuable cell source for the generation of iPS cells.
Induction of pluripotent stem cells from human third molar mesenchymal stromal cells.
Specimen part, Cell line
View SamplesWe explored the functional role of YAP in SCLC cells (SBC3 and SBC5) by YAP knockdown.
YAP and TAZ modulate cell phenotype in a subset of small cell lung cancer.
Cell line
View SamplesSteroid and xenobiotic receptor (SXR) and its murine ortholog pregnane X receptor (PXR) are nuclear receptors that are expressed mainly in the liver and the intestine. They function as xenobiotic sensors by inducing genes involved in detoxification and drug excretion. Recent evidence showed that SXR and PXR are also expressed in bone tissue where they mediate bone metabolism. Here we report that systemic deletion of PXR results in aging-dependent wearing of articular cartilage of knee joints. Histomorphometrical analysis showed remarkable reduction of width and an enlarged gap between femoral and tibial articular cartilage in PXR knockout mice. We hypothesized that genes induced by SXR in chondrocytes have a protective effect on articular cartilage and identified Fam20a (family with sequence similarity 20a) as an SXR-dependent gene induced by the known SXR ligands, rifampicin and vitamin K2. Lastly, we demonstrated the biological significance of Fam20a expression in chondrocytes by evaluating osteoarthritis-related gene expression of primary articular chondrocytes. Consistent with epidemiological findings, our findings indicate that SXR/PXR protects against aging-dependent wearing of articular cartilage and that ligands for SXR/PXR have potential role in preventing osteoarthritis caused by aging.
Pregnane X receptor knockout mice display aging-dependent wearing of articular cartilage.
Cell line
View SamplesTo investigate genes possibly regulated by TTF-1 in small cell lung cancer cell lines, we compared gene expression profiles of NCI-H209 and Lu139 cell lines electroporated with control and TTF-1 siRNAs.
An integrative transcriptome analysis reveals a functional role for thyroid transcription factor-1 in small cell lung cancer.
Cell line
View SamplesMED1/TRAP220, a subunit of the transcriptional Mediator/TRAP complex, is crucial for various biological events through its interaction with distinct activators such as nuclear receptors and GATA family activators. In hematopoiesis, MED1 plays a pivotal role in optimal nuclear receptor-mediated myelomonopoiesis and GATA-1-induced erythropoiesis. In this study, we present evidence that MED1 in stromal cells is involved in supporting hematopoietic stem and/or progenitor cells (HSPCs) through osteopontin (OPN) expression. We found that the proliferation of bone marrow (BM) cells cocultured with MED1 knockout (Med1-/-) mouse embryonic fibroblasts (MEFs) was significantly suppressed when compared to the control. Furthermore, the number of long-term culture-initiating cells (LTC-ICs) was attenuated for BM cells cocultured with Med1-/- MEFs. The vitamin D receptor (VDR)- and Runx2-mediated expression of OPN, as well as Mediator recruitment to the Opn promoter, was specifically attenuated in the Med1-/- MEFs. Addition of OPN to these MEFs restored the growth of cocultured BM cells and the number of LTC-ICs, both of which were attenuated by the addition of the anti-OPN antibody to Med1+/+ MEFs and to BM stromal cells. Consequently, MED1 in niche appears to play an important role in supporting HSPCs, by upregulating VDR- and Runx2-mediated transcription on the Opn promoter.
The transcriptional mediator subunit MED1/TRAP220 in stromal cells is involved in hematopoietic stem/progenitor cell support through osteopontin expression.
Specimen part
View SamplesTo identify gene expression profiles in those periodontitis-associated fibroblasts (PAFs) versus normal gingival fibroblasts to determine their molecular repertoire, and exploit it for therapeutic intervention.
Fibroblast VEGF-receptor 1 expression as molecular target in periodontitis.
Specimen part, Subject
View SamplesASCL1 is a master transcription factor for neuroendocrine differentiation. RNA-sequencing analysis on VMRC-LCD cells following ASCL1 knockdown revealed a subset of genes possibly regulated by ASCL1. Overall design: VMRC-LCD cells were transfected with siRNAs for ASCL1, and RNA-sequencing was performed using Illumina HiSeq.
An Integrative Analysis of Transcriptome and Epigenome Features of ASCL1-Positive Lung Adenocarcinomas.
Cell line, Subject
View SamplesTo investigate the roles of TAZ in lung fibroblasts, we compared the expression profiles of a lung fibroblast cell line, HFL-1, transfected with control siRNA and siTAZ. Overall design: We collected RNA from HFL-1 cells transfected with control siRNA and siTAZ. Two kinds of TAZ siRNAs (siTAZ #1 and siTAZ #2) were used. Two biological replicates (rep1 and rep2) were used for each condition.
TAZ contributes to pulmonary fibrosis by activating profibrotic functions of lung fibroblasts.
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