Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1000086 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25456200.fastq.gz | Fastqsanger.gz | |||
| SRR25456300.fastq.gz | Fastqsanger.gz | |||
| SRR25456400.fastq.gz | Fastqsanger.gz | |||
| SRR25456500.fastq.gz | Fastqsanger.gz | |||
| SRR25456600.fastq.gz | Fastqsanger.gz |
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Project description:Metastasis of Lung adenocarcinoma (LUAD) is a major cause of death in patients. Aryl hydrocarbon receptor (AHR) is an important transcription factor involved in the initiation and progression of lung cancer. Polo-like kinase 1 (PLK1), a serine/threonine kinase, is an oncogene that promotes the malignancy of multiple cancer types. Nonetheless, the interaction between these two factors and significance in lung cancer remains to be determined. Here, we demonstrate that PLK1 phosphorylates AHR at S489 in LUAD, which leads to epithelial-mesenchymal transition (EMT) and metastatic events. RNA-seq analyses show that type 2 deiodinase (DIO2) is responsible for EMT and enhanced metastatic potential. DIO2 converts tetraiodothyronine (T4) to triiodothyronine (T3), which then activates thyroid hormone signaling. In vitro and in vivo experiments demonstrate that treatment with T3 or T4 promotes the metastasis of LUAD, whereas depletion of DIO2 or deiodinase inhibitor disrupts this property. Taken together, our results identify the phosphorylation of AHR by PLK1 as a mechanism leading to the progression of LUAD and provide possible therapeutic interventions for this event.
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Project description:The monocarboxylate transporter 8 (Mct8) protein is a primary T4 and T3 (TH) transporter. Mutations of the MCT8-encoding, SLC16A2 gene alters thyroid function and thyroid hormone metabolism, and severely impairs neurodevelopment (Allan-Herndon-Dudley syndrome, AHDS). Mct8-deficient mice manifest thyroid alterations but lack neurological signs. It is thought that Mct8 deficiency in mice is compensated by T4 transport through the Slco1c1-encoded organic anion transporter polypeptide 1c1 (Oatp1c1). This allows local brain generation of sufficient T3 by the Dio2-encoded type 2 deiodinase (D2). The Slc16a2/Slco1c1 (MO) and Slc16a2/Dio2 (MD) double knock out mice lacking T4 and T3 transport, or T3 transport and T4 deiodination, would be more approriate models of AHDS. The goal of this work was to compare the cerebral hypothyroidism of systemic hypothyroidism (SH) caused by thyroid gland blockade with that present in the double KOs.
2020-12-15 | GSE155185 | GEO
Project description:The aim of this experiment was to explore transcriptomic changes in the gills of Altantic salmon (Salmo salar) following a model lab based parr smolt transformation from fresh water (FW) to salt water (SW). The process of smoltification (migration from FW to SW) is stimulated by long day photoperiod, which acts on the tissue-specific levels of active thyroid hormone (triiodothyronine, T3) through the expression of thyroid hormone type 2 deiodinase (dio2), responsible for conversion of inactive thyroxine (T4) to T3. To gain insight into the functional significance of dio2 induction, we performed a SW-challenge experiment in which we inhibited dio2 activity by addition of iopanoic acid (IOP) to the SW. We also assessed the ability of co-treatment with T3 to override IOP effects. Juvenile fish maintained in FW were subjected to a standard smolt photoperiod regime known to stimulate smoltification, after which they were randomly allocated to one of the four treatments: SW, SW+IOP, SW+IOP+T3 and FW as a control. Fish (n = 8-10 per treatment) were exposed to these conditions for 6 h and then sacrificed to obtain gill tissue for microarray analysis, carried out using a custom-designed Agilent oligonucleotide microarray platform Salar_2 (one glass slide with 4 x 44K arrays, Agilent design ID: 025520, array design A-MEXP-2065), developed and validated for Atlantic salmon (for details, see specific protocols) . In total, 36 hybridisations were performed on gills from individual fish, with 8-10 replicate fish per treatment. We identified 1939 genes whose expression was significantly increased or decreased by transfer from FW to SW. For a subset of 259 genes, this SW response was abolished if IOP was added to the SW, but maintained if T3 was also present during IOP treatment. This group of genes constitutes a candidate list, for which SW-inducibility appears to be dependent on locally mediated changes in gill T3 availability. The results of this experiment have been submitted for publication in Current Biology and are currently under review.
2015-03-19 | E-MTAB-3202 | biostudies-arrayexpress
Project description:Here we reveal a novel role for the circadian clock gene Bmal1 and Period2 in regulating the spatial organization of the cone opsins. Deletion of Bmal1 and Per2 have opposing effects on S-opsin expression and patterning of the cone photoreceptors is disrupted in cone specific knockouts of these genes. Using ChIP analysis we show that BMAL1 directly binds to the promoter region of the thyroid activating enzyme type II deiodinase (Dio2).
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Project description:Thyroid Stimulating Hormone Receptor signalling restores skeletal muscle stem cell regeneration in Duchenne muscular dystrophy
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2018-08-21 | GSE110372 | GEO
Project description:Thyroid hormone (TH) levels are low during development, and the deiodinases control TH signaling through tissue-specific activation or inactivation of TH. Here we studied human iPSC-derived hepatic organoids and identified a robust induction in DIO2 expression (the deiodinase that activates T4 to T3) that occurs in hepatoblasts. The surge in D2-T3 persists until the hepatoblasts differentiate into hepatocytes- or cholangiocytes-like cells, neither of which express DIO2. Preventing the induction of the D2-T3 signaling modified the expression of key transcription factors, decreased the number of hepatocyte-like cells by ~60%, and increased the number of cholangiocyte-like cells by ~55% without affecting the growth or the size of the mature liver organoid. Physiological levels of T3 could not fully restore the transition from hepatoblasts to mature cells. This indicates that the timed surge in D2-T3 signaling critically determines the fate of developing human hepatoblasts and the transcriptome of the maturing hepatocytes, with physiological and clinical implications for how the liver handles energy substrates.
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Project description:In the neonatal liver, a peak of type 2 deiodinase (D2) activity accelerates local T3 production and the expression of thyroid hormone (TH)-responsive genes. Here we show that this acute increase in T3 signaling permanently modifies hepatic gene expression. Liver-specific Dio2 inactivation (Alb-D2KO) transiently increased H3K9me3 levels during post-natal days 1-5 (P1-P5) in discrete chromatin areas, and methylation of 1,508 DNA sites (H-sites) that remained in the adult mouse liver. These sites were associated with 1,551 areas of reduced chromatin accessibility (RCA; Atac-seq) within core promoters and 2,426 within intergenic regions, with reduction in the expression of 1,525 genes (RNA-seq). There was strong correlation between H-sites and RCA sites (r=0.85; p<0.0002), suggesting a cause-effect relationship. The analysis of chromosome conformation capture (Hi-C) data revealed a set of 57 repressed genes that have a promoter RCA in close contact with an intergenic RCA ~300 Kbp apart, including Foxa2 that plays an important role during development. Thus, the post-natal surge in hepatic D2 activity and TH-signaling prevents discrete DNA methylation and modifies the transcriptome of the adult mouse. This explains how the systemic T3 hormone acts locally during development to define future chromatin accessibility and expression of critically relevant hepatic genes.
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Project description:In the neonatal liver, a peak of type 2 deiodinase (D2) activity accelerates local T3 production and the expression of thyroid hormone (TH)-responsive genes. Here we show that this acute increase in T3 signaling permanently modifies hepatic gene expression. Liver-specific Dio2 inactivation (Alb-D2KO) transiently increased H3K9me3 levels during post-natal days 1-5 (P1-P5) in discrete chromatin areas, and methylation of 1,508 DNA sites (H-sites) that remained in the adult mouse liver. These sites were associated with 1,551 areas of reduced chromatin accessibility (RCA; Atac-seq) within core promoters and 2,426 within intergenic regions, with reduction in the expression of 1,525 genes (RNA-seq). There was strong correlation between H-sites and RCA sites (r=0.85; p<0.0002), suggesting a cause-effect relationship. The analysis of chromosome conformation capture (Hi-C) data revealed a set of 57 repressed genes that have a promoter RCA in close contact with an intergenic RCA ~300 Kbp apart, including Foxa2 that plays an important role during development. Thus, the post-natal surge in hepatic D2 activity and TH-signaling prevents discrete DNA methylation and modifies the transcriptome of the adult mouse. This explains how the systemic T3 hormone acts locally during development to define future chromatin accessibility and expression of critically relevant hepatic genes.
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