This SuperSeries is composed of the SubSeries listed below.
Necroptosis microenvironment directs lineage commitment in liver cancer.
Sex, Cell line
View SamplesPrimary liver cancer represents a major health problem. It comprises hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), which differ markedly with regards to their morphology, metastatic potential and therapy response. Yet, molecular actors and tissue context that commit transformed hepatic cells towards HCC or ICC are largely unknown. Here, we report that the hepatic microenvironment epigenetically shapes lineage commitment in mosaic mouse models of liver tumourigenesis. While a necroptosis associated hepatic cytokine microenvironment determines ICC outgrowth from oncogenically transformed hepatocytes, hepatocytes harbouring identical oncogenic drivers give rise to HCC if surrounded by apoptotic hepatocytes. Epigenome and transcriptome profiling of murine HCC and ICC singled out Tbx3 and Prdm5 as major microenvironment-dependent and epigenetically regulated lineage commitment factors, a function conserved in humans. Together, our study provides unprecedented insights into lineage commitment in liver tumourigenesis and explains molecularly why common liver damaging risk factors can either lead to HCC or ICC.
Necroptosis microenvironment directs lineage commitment in liver cancer.
Sex
View SamplesPrimary liver cancer represents a major health problem. It comprises hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), which differ markedly with regards to their morphology, metastatic potential and therapy response. Yet, molecular actors and tissue context that commit transformed hepatic cells towards HCC or ICC are largely unknown. Here, we report that the hepatic microenvironment epigenetically shapes lineage commitment in mosaic mouse models of liver tumourigenesis. While a necroptosis associated hepatic cytokine microenvironment determines ICC outgrowth from oncogenically transformed hepatocytes, hepatocytes harbouring identical oncogenic drivers give rise to HCC if surrounded by apoptotic hepatocytes. Epigenome and transcriptome profiling of murine HCC and ICC singled out Tbx3 and Prdm5 as major microenvironment-dependent and epigenetically regulated lineage commitment factors, a function conserved in humans. Together, our study provides unprecedented insights into lineage commitment in liver tumourigenesis and explains molecularly why common liver damaging risk factors can either lead to HCC or ICC.
Necroptosis microenvironment directs lineage commitment in liver cancer.
Sex, Cell line
View SamplesSenescence can be transmitted in a paracrine way from cells undergoing Oncogene Induced Senescence (OIS) to nave normal cells. We define this phenomenon as paracrine senescence
A complex secretory program orchestrated by the inflammasome controls paracrine senescence.
Specimen part, Cell line
View SamplesNatural killer (NK) cells are lymphocytes that participate in immune responses through their cytotoxic activity and secretion of cytokines and chemokines. They can be activated by interaction with ligands on target cells or by soluble mediators such as cytokines. In addition, soluble HLA-G, a major histocompatibility complex molecule secreted by fetal trophoblast cells during early pregnancy, stimulates resting NK cells to secrete proinflammatory and proangiogenic factors. Human NK cells are abundant in uterus, where they remain after implantation. Soluble HLA-G is endocytosed into early endosomes of NK cells where its receptor, CD158d, initiates a signaling cascade through DNA-PKcs, Akt and NF-kB3. The physiological relevance of this endosomal signaling pathway, and how the fate and function of NK cells during early pregnancy is regulated, is unknown. Here we show that soluble agonists of CD158d trigger DNA damage response signaling and p21 (CIP1/WAF1) expression to promote senescence in primary NK cells. CD158d engagement resulted in morphological alterations in cell size and shape, chromatin remodeling, and survival in the absence of proliferation, all hallmarks of senescence. Microarray analysis revealed a senescence signature of upregulated genes upon sustained activation through CD158d. The proinflammatory and proangiogenic factors secreted by these metabolically active NK cells are part of a senescence associated secretory phenotype (SASP) that promoted tissue remodeling and angiogenesis as assessed by functional readouts of vascular permeability and endothelial cell tube formation. We propose that ligand-induced senescence is a molecular switch for the sustained activation of NK cells in response to soluble HLA-G for the purpose of remodeling the maternal vasculature in early pregnancy.
Cellular senescence induced by CD158d reprograms natural killer cells to promote vascular remodeling.
Specimen part, Treatment, Time
View SamplesThe SCH9 null strain has smaller cell size, grows at a slower rate and survives three times longer than wide-type yeast.
Comparative analyses of time-course gene expression profiles of the long-lived sch9Delta mutant.
Age
View SamplesThe three yeast mutants sch9, ras2, tor1 show extended chronological life span up to three folds.
Significant and systematic expression differentiation in long-lived yeast strains.
No sample metadata fields
View SamplesWe conducted a genome-wide expression analysis of wild-type males using three cell populations isolated from mitotic, meiotic and post-meiotic phases of spermatogenesis in Drosophila melanogaster. Our approach was to directly isolate testis regions enriched with RNAs from each of the three specific germline phases.
Stage-specific expression profiling of Drosophila spermatogenesis suggests that meiotic sex chromosome inactivation drives genomic relocation of testis-expressed genes.
Specimen part
View SamplesTGFbeta induces VSMC gene expression in human coronary artery smooth muscle cell (HCASM) Overall design: Subconfluent human coronary artery smooth muscle cells (HCASM) were starved overnight followed by TGFbeta treatment for 24 hours. RNA was then extracted for deep-sequencing.
Transforming growth factor β1 suppresses proinflammatory gene program independent of its regulation on vascular smooth muscle differentiation and autophagy.
Treatment, Subject
View SamplesTranscriptome analysis of RNA samples from riboflavin-depleted HEK293T cells.
Riboflavin Depletion Promotes Tumorigenesis in HEK293T and NIH3T3 Cells by Sustaining Cell Proliferation and Regulating Cell Cycle-Related Gene Transcription.
Cell line
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