The host antitumor immunity changes drastically during carcinogenesis. Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas is a precursor lesion of pancreatic cancer and progresses according to adenoma-carcinoma sequence. We found that the host antitumor immune reaction changes from an immune response to immune tolerance between intraductal papillary-mucinous adenoma (IPMA) and intraductal papillary-mucinous carcinoma (IPMC).
CXCL17 and ICAM2 are associated with a potential anti-tumor immune response in early intraepithelial stages of human pancreatic carcinogenesis.
Specimen part, Disease
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The histone variant H2A.Z promotes initiation of meiotic recombination in fission yeast.
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View SamplesMeiotic homologous recombination is a critical DNA-templated event for sexually-reproducing organisms. It is initiated by a programmed formation of DNA double strand breaks (DSBs), mainly formed at recombination hotspots, and is, like all other DNA-related processes, under great influence of chromatin structure. For example, local chromatin around hotspots directly impacts DSB formation. In addition, DSB is proposed to occur in a higher-order chromatin architecture termed axis-loop, in which many loops protrude from proteinaceous axis. Despite many recent insightful studies, still much remains unknown about how meiotic DSBs are generated in chromatin structure. Here, we show that the highly conserved histone H2A variant H2A.Z promotes meiotic DSB formation in fission yeast. Subsequent investigation revealed that H2A.Z is neither enriched around hotspots nor axis sites, and that transcript levels of DSB-promoting factors were maintained in the absence of H2A.Z. Instead, we found that H2A.Z facilitates chromatin binding of various proteins required for DSB formation. Strikingly, artificial tethering of one of such proteins, Rec10, to chromatin partially restored DSB reduction in H2A.Z-lacking cells. Based on these, we conclude that fission yeast H2A.Z promotes initiation of meiotic recombination partly through delivering DSB-related proteins onto chromatin.
The histone variant H2A.Z promotes initiation of meiotic recombination in fission yeast.
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View Samplesab and gd T cells originate from a common, multi-potential precursor population in the thymus, but the molecular mechanisms regulating this lineage fate decision process are unknown. We have identified Sox13 as a gd-specific gene in the immune system. Using Sox13 transgenic mice, we show that SOX13 promotes gd T cell development while opposing ab T cell differentiation. Conversely, mice deficient in Sox13 expression exhibited impaired development of gd T cells, but not ab T cells. One mechanism of SOX13 function is the inhibition of WNT/TCF signaling, suggesting that differential WNT/TCF activity is an essential parameter for this binary cell fate choice.
Regulation of gammadelta versus alphabeta T lymphocyte differentiation by the transcription factor SOX13.
Sex, Age, Specimen part
View SamplesExpression data from mice exposed to intermittent hypoxia and mice reared for 12 months. We used microarrays to analyze the transcriptome of hippocampus from mice exposed to intermittent hypoxia or aged mice.
Treatment of intermittent hypoxia increases phosphorylated tau in the hippocampus via biological processes common to aging.
Specimen part, Treatment
View SamplesGene expression is regulated by various mechanisms. One is gene silencing, which is caused by highly condensed chromatin structure. S. pombe Sgo2 is a protein involved in the spindle assembly checkpoint at centromere. In order to investigate the other functions of Sgo2, we analyzed the effect of Sgo2 deletion in global gene expressions.
Shugoshin forms a specialized chromatin domain at subtelomeres that regulates transcription and replication timing.
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View SamplesPartial induced pluripotent cells (iPSCs) are cell lines strayed from normal route from somatic cells to iPSCs and are immortalized. Mouse partial iPSCs are able to convert to real iPSCs by the exposure to 2i condition using MAPK and GSK3? inhibitors. However, the molecular mechanisms of this conversion are totally not known. Our piggyback vector mediated genome-wide screen revealed that Cnot2, one of core components of Ccr4-Not complex participates in this conversion. Subsequent analyses revealed other core components, i.e., Cnot1 and Cnot3 and Trim28 which is known to extensively share genomic binding sites with Cnot3 contribute to this conversion as well. Our bioinformatics analyses indicate that the major role of these factors in the conversion is the down-regulation of developmental genes in partial iPSCs.
Identification of Ccr4-not complex components as regulators of transition from partial to genuine induced pluripotent stem cells.
Sex, Specimen part
View SamplesTelomere erosion causes cell mortality, suggesting that longer telomeres allow greater number of cell division. In telomerase-positive human cancer cells, however, telomeres are often kept shorter than the surrounding normal tissues. Recently, we have shown that telomere elongation in cancer cells represses innate immune genes and promotes their differentiation in vivo. This implies that short telomeres contribute to cancer malignancy, but it is unclear how such genetic repression is caused by long telomeres. Here we report that telomeric repeat-containing RNA (TERRA) induces genome-wide alteration of gene expression in telomere-elongated cancer cells in vivo. Using three different cell lines, we found that G4 forming oligonucleotide repressed innate immune genes in vivo 3D culture conditions. Most of the suppressed genes belonged to innate immune system categories and were upregulated in various cancers. We propose that TERRA G4 counteracts cancer malignancy through suppression of innate immune genes.
Telomeric repeat-containing RNA/G-quadruplex-forming sequences cause genome-wide alteration of gene expression in human cancer cells in vivo.
Cell line, Treatment
View SamplesTelomere erosion causes cell mortality, suggesting that longer telomeres allow greater number of cell division. In telomerase-positive human cancer cells, however, telomeres are often kept shorter than the surrounding normal tissues. Recently, we have shown that telomere elongation in cancer cells represses innate immune genes and promotes their differentiation in vivo. This implies that short telomeres contribute to cancer malignancy, but it is unclear how such genetic repression is caused by long telomeres. Here we report that telomeric repeat-containing RNA (TERRA) induces genome-wide alteration of gene expression in telomere-elongated cancer cells in vivo. Using three different cell lines, we found that telomere elongation upregulates TERRA and downregulates innate immune genes in vivo xenograft tumors. Most of the suppressed genes belonged to innate immune system categories and were upregulated in various cancers. We propose that TERRA G4 counteracts cancer malignancy through suppression of innate immune genes.
Telomeric repeat-containing RNA/G-quadruplex-forming sequences cause genome-wide alteration of gene expression in human cancer cells in vivo.
Disease, Cell line
View SamplesLow-intensity pulsed ultrasound (LIPUS) has been applied as a therapeutic adjunct to promote fracture healing. However, the detailed molecular mechanisms by which LIPUS promotes bone fracture healing have not yet been fully elucidated.
Genetic response to low‑intensity ultrasound on mouse ST2 bone marrow stromal cells.
Specimen part
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