Prdx2 is the thioredoxin-dependent peroxidase that reduces H2O2 using reducing power NADPH in the presence of thioredoxin and thioredoxin reductase. Prdx2 plays an important role in growth. factor signaling in mammlian cells. Therefore, we examined the gene expression in colon adenocarcinoma cell line HT29 after Prdx2 depletion. Prdx2 depletion resulted in a significant alteration on gene expression, including protein synthesis, metabolisms, and cell cycle. Overall design: Control-siRNA-transfected versus PRDX2-siRNA-transfected HT29 and SW480 cells
Interaction of tankyrase and peroxiredoxin II is indispensable for the survival of colorectal cancer cells.
Cell line, Subject
View SamplesReduced or absent cytotrophoblast invasion of the maternal uterine spiral arteries is a common clinical finding in studies of pregnancies complicated by preeclampsia, suggesting that the mechanisms behind invasion of these cells is perturbed. The placenta initially develops in a low oxygen environment of 1-2% oxygen until after the 10th week of pregnancy. During this time oxygen concentration exerts a major influence over trophoblast activity and, in vitro, hypoxia inducible factors are proposed to be one of many key regulators of first trimester trophoblast behaviour. We used a global gene expression microarray approach to identify signalling pathways involved in invasion of the first trimester trophoblast cell line HTR8/SVneo under hypoxic conditions where HIF-1 was active. Additionally, first trimester placental samples from different gestational age groups were labelled with anti HIF-1 and HIF-2 to evaluate whether HIFs are differentially expressed and localised across the period of development characterised by hypoxia (6-8 weeks) and maternal blood perfusion (10-12 weeks). Eighty-eight genes were differentially expressed between cells cultured in 1% oxygen (where HIF-1 was localised to the nucleus) and 5% oxygen (where HIF-1 was cytoplasmic). 65% of the genes were predicted to contain HIF-1:ARNT transcription factor binding sites. Increased nuclear localisation of HIF-1 was seen in extravillous cytotrophoblasts in early first trimester compared with late, while cellular expression of HIF-2 in the villous stroma was higher in late first trimester. While HIFs and their downstream targets are clearly induced in trophoblasts during early placental development, and in vitro hypoxic conditions, the mechanism and pathways by which invasion is increased under hypoxic conditions is not clear from the gene expression profile. Further insight beyond the transcription level is required to fully understand this complex phenomenon.
Hypoxia induced HIF-1/HIF-2 activity alters trophoblast transcriptional regulation and promotes invasion.
Cell line, Treatment
View SamplesAnalysis of mouse placenta retrieved at day 18.5pc from vitamin D (1,25-dihydroxyvitamin D3) receptor (Vdr) knockout, heterozygous and wild-type mice. Results provide insight into the molecular mechanisms underlying the effect of vitamin D on placental function.
Vitamin D Receptor Gene Ablation in the Conceptus Has Limited Effects on Placental Morphology, Function and Pregnancy Outcome.
Specimen part
View SamplesAlthough cancer stem cells (CSCs) are thought to be responsible for tumor recurrence and resistance to chemotherapy, CSC-related research and drug development have been hampered by the limited supply of patient-derived diverse CSCs. Here, we developed a functional polymer thin film (PTF) platform that promotes conversion of human cancer cell lines to highly tumorigenic spheroids without the use of biochemical or genetic manipulations. Culturing various human cancer cells on the specific PTF, poly(2,4,6,8-tetravinyl-2,4,6,8-tetramethyl cyclotetrasiloxane) (pV4D4), gave rise to numerous multicellular spheroids within 24 hours, with high efficiency and reproducibility. Cancer cells in the resulting spheroids showed an enormous increase in the expression of CSC-associated genes and acquired dramatically increased drug resistance compared with monolayer-cultured controls. These spheroids also showed greatly enhanced xenograft tumor-forming ability and metastasis capacity in nude mice. By enabling the generation of tumorigenic spheroids as a patient-derived CSC substitute, the surface platform described here will likely contribute to CSC-related basic research and drug development. Overall design: mRNA profiles of 8 day-SKOV3-ssiCSC spheroids and 2D-cultured SKOV3 control were generated by deep sequencing, in duplicate, using Hiseq-2500.
Polymer Thin Film-Induced Tumor Spheroids Acquire Cancer Stem Cell-like Properties.
Specimen part, Subject
View Samplesnc886 is a 101 nucleotides long non-coding RNA that is also known as a precursor microRNA or a vault RNA. nc886 has been suggested to be a tumor suppressor, mainly inferred by its expression pattern as well as its genomic location at human chromosome 5q31, a locus for a tumor suppressor gene(s).
Epigenetic silencing of the non-coding RNA nc886 provokes oncogenes during human esophageal tumorigenesis.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
An integrated systems biology approach identifies positive cofactor 4 as a factor that increases reprogramming efficiency.
Sex, Specimen part
View SamplesMultipotent spermatogonial stem cells (mSSCs) derived from SSCs are a potential new source of individualized pluripotent cells in regenerate medicine such as ESCs. We hypothesized that the culture-induced reprogramming of SSCs was mediated by a mechanism different from that of iPS, and was due to up-regulation of specific pluripotency-related genes during cultivation. Through a comparative analysis of expression profile data, we try to find cell reprogramming candidate factors from mouse spermatogonial stem cells. We used microarrays to analyze the gene expression profiles of culture-induced reprogramming converting unipotent spermatogonial stem cells to pluripotent spermatogonial stem cells.
An integrated systems biology approach identifies positive cofactor 4 as a factor that increases reprogramming efficiency.
Sex, Specimen part
View SamplesSpermatogonial stem cells (SSCs) can spontaneously dedifferentiate into embryonic stem cell (ESC)-like cells, which are designated as multipotent SSCs (mSSCs), without ectopic expression of reprogramming factors. SSCs express key OSKM reprogramming factors at some levels, and do not require ectopic expression of any gene for the acquisition of pluripotency during reprogramming to mSSCs. Therefore, we reasoned that additional factors are required to regulate SSC reprogramming. In this study, we first compared the expression of reprogramming signature genes among somatic cells, iPSC, SSCs, mSSCs, and partially reprogramed cells, and found that they appear to have similar pluripotency states, whereas their transcriptional program differs. We developed a systems biology approach to prioritise genes for pluripotency regulatory factors by integrating transcriptome and interactome data on the genome-wide functional network. Then, we performed a series of systematic gene prioritisation steps and identified 53 candidates, which included some known reprogramming factors. We experimentally validated one particular candidate, Positive cofactor 4 (Pc4), which was expressed in PSCs and yielded a positive RNA interference (RNAi) response in an Oct4 reporter assay. We demonstrated that Pc4 enhanced the efficiency of OSKM-mediated reprogramming by promoting the transcriptional activity of key pluripotency factors, and by regulating the expression of many protein- and miRNA-encoding genes involved in reprogramming and somatic cell-specific genes. Overall design: Pc4-overexpressing mESC lines were established by Venus (YFP)-expressing lentiviral transfection. The mESCs were split at a density of 2 ´ 104 cells onto fresh MEF feeder cells seeded into a 6 well dish (containing mESC growth medium) with virus particles, and 25 µg/ml polybrene (Sigma Aldrich) was added. After 24 h, the medium was replaced with fresh growth medium. After 4 days later, mESC colonies expressing YFP were picked and replated. Three different Pc4-overexpressing mESC lines were established.
An integrated systems biology approach identifies positive cofactor 4 as a factor that increases reprogramming efficiency.
Specimen part, Cell line, Subject
View SamplesThe aim of this study was to evaluate and compare the gene expression profiles of dental follicle and periodontal ligament in humans, which can possibly explain their functions of dental follicle and PDL such as eruption coordination and stress resorption. That may apply this information to clinical problem like eruption disturbance and to periodontal tissue engineering.
Comparative gene-expression analysis of the dental follicle and periodontal ligament in humans.
Specimen part
View SamplesThe concept of dedifferentiation of somatic cells into pluripotent stem cells has opened a new era in regenerative medicine. Viral transduction of defined factors has successfully achieved pluripotency derived from somatic cells. However, during the generation process of induced pluripotent stem (iPS) cells, genetic integration of certain factors may cause mutagenesis or tumorigenicity, which limits further application. Therefore, there is currently ongoing an extensive search for new methods such as transient gene delivery and oocyte-free and non-viral inducers like small molecules. Here we show that the transient delivery of embryonic stem (ES) cell-derived soluble proteins enables dedifferentiation of mouse adult somatic cells converting them into pluripotent stem cells without the introduction of certain transcription factors or genetic manipulation. During the dedifferentiation, global gene expression patterns and epigenetic status were converted from the somatic to the ES-equivalent status. Dedifferentiated somatic cells were morphologically, biologically and functionally indistinguishable from ES cells. Furthermore, the dedifferentiated cells possessed in vivo differentiation and development potential. Our results provide an alternative and safe strategy for dedifferentiation of somatic cells that can be used to facilitate pluripotent stem cell-based cell therapy.
Induction of pluripotent stem cells from adult somatic cells by protein-based reprogramming without genetic manipulation.
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