Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1044078 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26918602.fastq.gz | Fastqsanger.gz | |||
| SRR26918603.fastq.gz | Fastqsanger.gz | |||
| SRR26918604.fastq.gz | Fastqsanger.gz | |||
| SRR26918605.fastq.gz | Fastqsanger.gz | |||
| SRR26918606.fastq.gz | Fastqsanger.gz |
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Project description:Background: Thyroxine (T4) is generally considered to be a pro-hormone that requires conversion to 3,5,3’-triiodothyronine (T3) to exert biological activity. Although evidence suggests that T4 has intrinsic activity, it is questionable if this activity has any physiological relevance. Methods: To answer this question, triple KO mice (Triples) that cannot express the types 1 (D1) and 2 (D2) deiodinase and the Pax8 genes were generated. Thus they lack a thyroid and cannot convert T4 to T3. Triples were injected on alternate days with either vehicle or physiological doses of T4, T3 or T3+T4 from postnatal days 2 to 14. They were euthanized at P15 and RNA-seq was employed to profile gene expression in liver. In another experiment, Pax8KO mice were injected with T3, T4 or T4 +T3, and growth rate and survival to P84 were determined. Results: The growth retardation of Triples was not improved by either T3 or T4 alone but was significantly improved by T4+T3. In liver, T4 significantly regulated the expression of genes that were also regulated by T3, but the proportion of genes that were negatively regulated was higher in mice treated with T4 than with T3. Treatment with T4+T3 identified genes that were regulated synergistically by T3 and T4, and genes that were regulated only by T4+T3. Analysis of these genes revealed enrichment in mechanisms related to cell proliferation and cholesterol physiology, suggesting a unique contribution of T4 to these biological functions. Pax8KO mice all survived to P84 when injected with T4 or T4+T3 but survival rate with T3 was 50% and 10% at 3.5 and 12 weeks of life, respectively. Conclusion: T4 has intrinsic activity in vivo and is critical for survival and growth. At a physiological level, T4 per se can up- or down-regulate many T3 target genes in the neonatal liver. While most of these genes are also regulated by T3, subsets respond exclusively to T4 or demonstrate enhanced or normalized expression only in the presence of both hormones. These studies demonstrate for the first time a complex dependency on both T4 and T3 for normal mammalian growth and development.
2021-03-31 | GSE154156 | GEO
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:Thyroid hormones (TH), thyroxine (T4) and 3, 5, 3’-triiodothyronine (T3), play crucial roles in regulation of growth, development and metabolism in vertebrates and their action are targets for endocrine disruptive agents. Perturbations in TH action can contribute to the development of disease states and the U.S. Environmental Protection Agency is developing a high throughput screen using TH-dependent amphibian metamorphosis as an assay platform. Currently this methodology relies on external morphological endpoints and changes in central thyroid axis parameters. However, exposure-related changes in gene expression in TH-sensitive tissue types that occur over shorter time frames have the potential to augment this screen. This study aims to characterize and identify molecular markers in the tadpole brain. Using a combination of cDNA array analysis and real time quantitative polymerase chain reaction (QPCR), we examine the brain of tadpoles following 96 hours of continuous exposure to T3, T4, methimazole, propylthiouracil, or perchlorate. This tissue was more sensitive to T4 rather than T3, even when differences in biological activity were taken into account. This implies that a simple conversion of T4 to T3 cannot fully account for T4 effects on the brain and suggests distinctive mechanisms of action for the two THs. While the brain shows gene expression alterations for methimazole and propylthiouracil, the environmental contaminant, perchlorate, had the greatest effect on the levels of mRNAs encoding proteins important in neural development and function. Our data identify gene expression profiles that can serve as exposure indicators of these chemicals. Keywords: dose response
2007-05-12 | GSE7057 | GEO
Project description:Thyroid hormones (TH), thyroxine (T4) and 3, 5, 3’-triiodothyronine (T3), play crucial roles in regulation of growth, development and metabolism in vertebrates and their action are targets for endocrine disruptive agents. Perturbations in TH action can contribute to the development of disease states and the U.S. Environmental Protection Agency is developing a high throughput screen using TH-dependent amphibian metamorphosis as an assay platform. Currently this methodology relies on external morphological endpoints and changes in central thyroid axis parameters. However, exposure-related changes in gene expression in TH-sensitive tissue types that occur over shorter time frames have the potential to augment this screen. This study aims to characterize and identify molecular markers in the tadpole brain. Using a combination of cDNA array analysis and real time quantitative polymerase chain reaction (QPCR), we examine the brain of tadpoles following 96 hours of continuous exposure to T3, T4, methimazole, propylthiouracil, or perchlorate. This tissue was more sensitive to T4 rather than T3, even when differences in biological activity were taken into account. This implies that a simple conversion of T4 to T3 cannot fully account for T4 effects on the brain and suggests distinctive mechanisms of action for the two THs. While the brain shows gene expression alterations for methimazole and propylthiouracil, the environmental contaminant, perchlorate, had the greatest effect on the levels of mRNAs encoding proteins important in neural development and function. Our data identify gene expression profiles that can serve as exposure indicators of these chemicals. Keywords: time course
2007-05-12 | GSE6964 | GEO
Project description:Astrocytes mediate the action of thyroid hormone in the brain on other neural cells through the production of the active hormone triiodothyronine (T3) from its precursor thyroxine (T4). T3 has also many effects on the astrocytes in vivo and in culture, but whether these actions are directly mediated by transcriptional regulation is not clear. In this work, we have analyzed the genomic response to T3 of cultured astrocytes isolated from the postnatal mouse cerebral cortex, using RNA sequencing. Cultured astrocytes express relevant genes of thyroid hormone metabolism and action encoding type 2 deiodinase (Dio2), Mct8 transporter (Slc16a2), T3 receptors (Thra1 and Thrb), and nuclear corepressor (Ncor1) and coactivator (Ncoa1). T3 changed the expression of 668 genes (4.5% of expressed genes), of which 117 genes (0.8% of expressed genes) were primary, transcriptional responses. The Wnt and Notch pathways were down-regulated at the post-transcriptional level. Comparison with the effect of T3 on astrocyte-enriched genes in mixed cerebrocortical cultures isolated from fetal cortex revealed that the response to T3 is influenced by the degree of astrocyte maturation, and that in agreement with its physiological effects, T3 promotes the transition between the fetal and adult patterns of gene expression.
2018-08-21 | GSE110372 | GEO
Project description:Purpose: sRNA-sequencing of mature and intermediate gonadal tissue in order to identify the differential expression of miRNAs during male to female (i.e. protandrous) sex transition Methods: Total RNA was extracted and sRNA was purified. cDNA libraries were constructed using a high definition adapter protocol (Xu et al. 2015). 50 bp sequencing was performed on Illumina's HiSeq 2500 at the Earlham Institute, Norwich, UK. Sequenced data was trimmed for adapters and filtered to remove very short and low complexity sequences. miRBase animal miRNA precursor sequences were mapped against the Asian seabass genome in order to generate a set of putative miRNA precursors. Putative precursor molecules with aligning mature miRBase miRNA(s) and forming a valid pre-miRNA hairpin structure were annotated as valid precursor miRNAs. Novel precursor and mature miRNAs were annotated using a combination of published algorithms and manual checking to ensure consistency with canonical miRNA biogenesis criteria. The alignment of sequenced reads against a non-redundant miRNA precursor set was used to determine raw read counts of mature miRNAs. Differential expression analysis was performed in order to identify differentially expressed mature miRNAs between conditions. Results: We detect 156, 71, 122, 151, 171 and 155 differentially expressed miRNA for the testis -> T1/T2, T1/T2 -> T3/T4, T3/T4 -> ovary, testis -> T3/T4, T1/T2 -> ovary and the testis->ovary comparisons respectively Conclusions: There is substantial differential expression of miRNAs at every stage of gonadal change in the Asian seabass during the sex transition process
2022-10-20 | GSE122720 | GEO
Project description:The thyroid hormone receptor (TR) has been proposed to regulate target genes in the absence of triiodothyronine (T3), through the recruitment of the corepressors, NCoR and SMRT. NCoR and SMRT may thus play a key role in both hypothyroidism and resistance to thyroid hormone, though this has never been tested in vivo. To accomplish this we developed mice that express in the liver a NCoR protein (L-NCoR∆ID) that cannot interact with the TR. L-NCoR∆ID mice develop normally, however when made hypothyroid the repression of many positively regulated T3-target genes is abrogated, demonstrating that NCoR plays a specific and sufficient role in repression by the unliganded TR. Remarkably, in the euthyroid state, expression of many T3-targets are also upregulated in L-NCoR∆ID mice, demonstrating that NCoR also determines the magnitude of the response to T3 in euthyroid animals. While positive T3 targets were upregulated in L-NCoR∆ID mice in the hypo and euthyroid state there was less effect seen on negatively regulated T3 target genes. Thus, NCoR is a specific regulator of T3-action in vivo and mediates the activity of the unliganded TR. Furthermore, NCoR may play a key role in determining the differences in individual responses to similar levels of circulating T3. Keywords: NCoR, thyroid hormone signaling, mouse liver, DNA Microarray
2008-12-04 | GSE10001 | GEO
Project description:We sequenced 12 ATAC-Seq lbraries from four biological replicates before (T1) and after the onset of maturation (T2, T3, T4) from liver. To characterise changes in chromatin state following long light initiation, we defined differentially accessible regions (DARs) where mapping counts differed significantly between T1 and other time points. This revealed a strong early remodelling in the chromatin state landscape, as most DARs were observed at T2 (n=1501) before decreasing in stepwise fashion at T3 (n=477) and T4. The majority of DARs (n=1036 or 57%) exhibit reduced accessibility at T2 compared with T1 and subsequently remained unchanged at later time points (Fig. 5a; Supplementary Figure S14). Similarly, regions that gained accessibility at T2 (n=696 or 38%) also remained unchanged at later timepoints. This left less than 10% of DARs (n=99) that displayed an oscillating pattern following the onset of the maturation. Together, this revealed the ATAC-seq signatures were predominantly stable chromatin state changes.
2020-08-28 | GSE156998 | GEO
Project description:Thyroid hormones T3 and T4 play a crucial role in the regulation of vertebrate metabolism. The thyroglobulin (Tg) protein is key to thyroid hormone synthesis, and its structure is conserved among vertebrates. TgG is delivered through the secretory pathway to the lumen of the thyroid gland, where it is iodinated at specific tyrosine sites to form mono- or di-iodotyrosine, which combine to produce T3 and T4, respectively. The formation of these hormones depends on the precise 3D structure of thyroglobulin, which has remained unknown despite decades of research on this protein. Here, we present the cryo-electron microscopy structure of human thyroglobulin, to a global resolution of 3.2 Å. Our results offer structural insight into thyroid hormonogenesis and provide a framework to understand hundreds of clinically relevant mutations. The structure of hTg contributes to a better understanding and potentially improved treatment of thyroid hypothyroidism, thyroid cancer and other Tg disorders.
2022-02-24 | PXD018452 | Pride
Project description:mRNA was sampled during exponential growth phase (T1), beginning of stationary/production phase (T2), middle of production phase (T3-T4) and end of production phase (T5-T6) strains: Y. lipolytica Af4 - DHA producer (Gemperlein et al., 2019) and Y. lipolytica Po1h - wild type
2024-01-01 | GSE224529 | GEO