Inflammatory hepatocellular adenomas (IHCA) are benign liver tumours defined by the presence of inflammatory infiltrates and by the elevated expression of inflammatory proteins in tumour hepatocytes1,2. Here we show a striking activation of the IL6 signalling pathway in this tumour type, and sequencing candidate genes pinpointed this response to somatic gain-of-function mutations in the IL6ST gene that encodes the signalling co-receptor gp130. Indeed, ~70% of IHCA harbour small in-frame deletions that target the binding site of gp130 for IL6, and expression of the most frequent gp130 mutant, Delta-STVY190, in hepatocellular cells activates STAT3 in absence of ligand. Further, analysis of hepatocellular carcinomas revealed rare gp130 alterations always accompanied by -catenin-activating mutations, suggesting a cooperative effect of these signalling pathways in the malignant conversion of hepatocytes. The recurrent gain-of-function gp130 mutations in these human hepatocellular adenomas explains their inflammatory phenotype, and suggest that similar alterations may occur in other inflammatory epithelial tumours with STAT3 activation.
Frequent in-frame somatic deletions activate gp130 in inflammatory hepatocellular tumours.
Sex, Specimen part, Disease
View SamplesThe demyelination (dmy) rat is a unique spontaneous myelin mutation that exhibits severe myelin breakdown with a late onset of clinical signs. The causative autosomal recessive mutation has been identified at the MRS2 magnesium transporter (Mrs2) gene, which encodes an essential component of the major Mg2+ influx system in mitochondria.
Enhanced Expression of Trib3 during the Development of Myelin Breakdown in dmy Myelin Mutant Rats.
Specimen part
View SamplesTHO2 and HPR1 proteins were co-depleted from Drosophila S2 cells and their role in mRNA export analysed by comparing total RNA and cytoplasmic RNA
The superhelical TPR-repeat domain of O-linked GlcNAc transferase exhibits structural similarities to importin alpha.
Cell line
View SamplesHomeostatic programs maintain equilibrium between immune protection, and selftolerance. Such mechanisms impact autoimmunity and tumor formation, respectively. How tissue homeostasis is maintained, and impacts tumor surveillance is unknown. Here we identify that mononuclear phagocytes share conserved programming during homeostatic differentiation, and entry into tissue. IFN is necessary and sufficient to induce these transcripts, revealing a key instructive role. Remarkably, homeostatic and IFN-dependent programs enrich across primary human tumors, including melanoma, and stratify metastatic melanoma survival. Single-cell RNA-sequencing reveals enrichment of these modules in monocytes and DCs in human metastatic melanoma. Suppressor-of-cytokine-2 (SOCS2), a highly conserved transcript in this program is induced by IFN, and expressed in mononuclear phagocytes infiltrating primary melanoma. SOCS2 limits DC adaptive anti-tumoral immunity and T cell priming in vivo, indicating a critical regulatory role. Our findings link homeostasis in peripheral tissue to anti-tumoral immunity and escape, revealing coopting of tissue-specific immune development in the tumor microenvironment.
IFNγ-Dependent Tissue-Immune Homeostasis Is Co-opted in the Tumor Microenvironment.
Specimen part, Disease, Disease stage
View SamplesPAX2 is one of nine PAX genes that regulate tissue development and cellular differentiation in embryos. PAX2 promotes cell proliferation, oncogenic transformation, cell lineage specification, migration, and survival. In our previous study, we found that PAX2 is highly expressed in low-grade ovarian serous carcinoma, but its expression in clear cell, endometrioid, and mucinous cell ovarian carcinomas have not been studied. More importantly, the functional role of PAX2 in ovarian cancer is not known.
PAX2 Expression in Ovarian Cancer.
Cell line, Treatment
View SamplesIn order to investigate the function of heme in the regulation of gene expression, we herein examined variations in mRNA levels in ALA-treated cells from control conditions. A comprehensive anal- ysis by RNA sequencing showed marked changes in the expression of various genes. Among the different amounts of mRNA, we identified the novel heme-inducible protein, SRRD. The plant ho- mologue Sensitivity to Red Light Reduced (SRR1) was previously reported to be involved in the regulation of the circadian clock and phytochrome B signaling in Arabidopsis thaliana. We found that SRRD regulated not only heme biosynthesis, but also the expression of clock genes. The involvement of SRRD in the prolif- eration of cells was also demonstrated. Overall design: Examination of ALA-treated versus untreated NIH3T3 cells.
The novel heme-dependent inducible protein, SRRD regulates heme biosynthesis and circadian rhythms.
Cell line, Subject
View SamplesWe used microarrays to analyze the gene expression profile of CD34+CD45RA+CD7+, CD34+CD45RA+CD10+CD19- and CD34+CD45+CD7-CD10-CD19- HPCs isolated from umbilical cord blood
Molecular characterization of early human T/NK and B-lymphoid progenitor cells in umbilical cord blood.
Specimen part
View SamplesWe transduced clonally MLL-AF9 leukemia cells expressing cas9 with sgRNA targeting the jumonji and zinc finger domains of JMJD1C. GFP (MLL-AF9) and TdTomato (sgRNA) double positive cells were sorted on Day 6 after transduction. Total RNA was isolated followed by mRNA selection. cDNA libraries were generated and NextGen Sequencing was performed. Overall design: We performed RNA-seq in mouse MLL-AF9 cas9 cells harboring sgRNA against jumonji and zinc finger domains of JMJD1C or renilla.
Critical role of Jumonji domain of JMJD1C in MLL-rearranged leukemia.
Specimen part, Subject
View SamplesWe performed single-cell sequencing on mouse MLL-AF9-cas9 leukemia cells 7 days after transduction with sgRNA against Renilla or JMJD1C JmjC domain. We revealed heterogeneity within each population. Overall design: We performed single-cell sequencing on mouse MLL-AF9 cells harboring JMJD1C sgRNA targeting jumonji domain or renilla control sgRNA.
Critical role of Jumonji domain of JMJD1C in MLL-rearranged leukemia.
Specimen part, Subject
View SamplesNIH3T3 in the middle of G0 to G1 transion consists of the cells which is still staying G0 phase and the cells which enters G1. Monitoring the expressions of p27 and Cdt1 enables to distinguish these two; p27+/Cdt1+ cells as the cells in G0 phase and p27-Cdt1+ cells as G1 phase
A novel cell-cycle-indicator, mVenus-p27K-, identifies quiescent cells and visualizes G0-G1 transition.
Cell line
View Samples