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Biphasic expression of thyroid hormone receptor TRb1 in mammalian retina and anterior ocular tissues

ABSTRACT: Biphasic expression of thyroid hormone receptor TRb1 in mammalian retina and anterior ocular tissues

PROVIDER: PRJNA932810 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23374200.fastq.gz	Fastqsanger.gz
	SRR23374201.fastq.gz	Fastqsanger.gz
	SRR23374202.fastq.gz	Fastqsanger.gz
	SRR23374203.fastq.gz	Fastqsanger.gz
	SRR23374204.fastq.gz	Fastqsanger.gz

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Biphasic expression of thyroid hormone receptor TRb1 in mammalian retina and anterior ocular tissues

Project description:Purpose: Using customized RNA-sequencing analyses to reveal notably different expression profiles of TRb1 and TRb2 in mouse retina. Method and Results: TRb2 peaks early whereas TRb1 peaks later during retinal maturation or during later differentiation. TRb1-knockout mice displayed only minor changes in opsin photopigment expression and normal electroretinogram responses, indicating that TRb2 and TRb1 are not functionally equivalent in cone differentiation. The biphasic expression patterns of TRb1 and TRb2 suggest versatile functions for thyroid hormone in retinal and non-neural ocular development.

2023-04-18 | GSE224863 | GEO

Biphasic expression of thyroid hormone receptor TRβ1 in mammalian retina and anterior ocular tissues.

Project description:The retina is increasingly recognized as a target of thyroid hormone. We previously reported critical functions for thyroid hormone receptor TRβ2, encoded by Thrb, in cones, the photoreceptors that mediate color vision. TRβ1, another Thrb receptor isoform, is widely expressed in other tissues but little studied in the retina. Here, we investigate these N-terminal isoforms by RNA-sequencing analysis and reveal a striking biphasic profile for TRβ1 in mouse and human retina. In contrast to the early TRβ2 peak, TRβ1 peaks later during retinal maturation or later differentiation of human retinal organoids. This switch in receptor expression profiles was confirmed using lacZ reporter mice. TRβ1 localized in cones, amacrine cells and ganglion cells in contrast to the restricted expression of TRβ2 in cones. Intriguingly, TRβ1 was also detected in the retinal pigmented epithelium and in anterior structures in the ciliary margin zone, ciliary body and iris, suggesting novel functions in non-retinal eye tissues. Although TRβ1 was detected in cones, TRβ1-knockout mice displayed only minor changes in opsin photopigment expression and normal electroretinogram responses. Our results suggest that strikingly different temporal and cell-specific controls over TRβ1 and TRβ2 expression may underlie thyroid hormone actions in a range of ocular cell types. The TRβ1 expression pattern suggests novel functions in retinal and non-neural ocular tissues.

| S-EPMC10076699 | biostudies-literature

Bulk RNA-seq analysis of developing ocular anterior segments from wildtype and Col4a1 mutant mice

Project description:COL4A1 mutations cause Gould syndrome, a multi-system disorder which is characterized by a broad range of cerebrovascular, ocular, muscular, renal, or cardiac manifestations. To investigate the patheogenic mechanism of Col4a1 mutations in ocular anterior segment dysgenesis, we used a Col4a1 mutant mouse model that recapitulate many aspects of the pathophysiological hallmarks of Gould syndrome including anterior segment dysgenesis. We then isolated developing anterior segments from wildtype and mutant mice and performed differntial expression analysis using bulk RNAseq.

2022-05-18 | GSE202801 | GEO

Intra-ocular dendritic cells characterize HLA-B27-associated acute anterior uveitis

Project description:Uveitis describes a heterogeneous group of inflammatory eye diseases characterized by infiltration of leukocytes into the uveal tissues. uveitis associated with the HLA haplotype B27 (HLA-B27) is a common subtype of uveitis and a prototypical ocular immune-mediated disease. Local immune mechanisms driving human uveitis are poorly characterized mainly due to the limited available biomaterial and subsequent technical limitations. Here, we provide the first high-resolution characterization of intraocular leukocytes in HLA-B27 positive (n=3) and negative (n=2) anterior uveitis and an infectious endophthalmitis control (n=1) by combining single cell RNA-sequencing with flow cytometry and protein analysis. Ocular cell infiltrates consisted primarily of lymphocytes in both subtypes of uveitis and of myeloid cells in infectious endophthalmitis. HLA-B27 positive uveitis exclusively featured a plasmacytoid and classical dendritic cells (cDC) infiltrate. Moreover, cDCs were central in predicted local cell-cell communication. This suggests a unique pattern of ocular leukocyte infiltration in HLA-B27 positive uveitis with relevance of dendritic cells.

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Characterizing the TRb1 cistrome in mouse liver

Project description:ChIP-seq data from mouse liver over-expressing GFP and fed a PTU diet and treated with saline, or overexpressing biotinylated TRb1 and GFP and fed a PTU diet, treated with either saline or T3 Mouse liver was infected with adenovirus that either expressed only GFP or GFP and biotinylated TRb1 and were fed a PTU diet, followed by injections with only saline (GFP-only livers) or with saline or T3 (Biotinylated-TRb1 and GFP livers). ChIP assays were performed using streptavidin agarose to capture biotinylated TRb1 followed by library construction and sequencing.

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Project description:The anterior segment of the eye consists of the cornea, iris, ciliary body, crystalline lens and aqueous humor outflow pathways. Together, these tissues are essential for the proper functioning of the eye. Disorders of vision have been ascribed to defects in all of them; some, including glaucoma and cataract, are among the most prevalent causes of blindness. To characterize the cell types that comprise these tissues, we generated an anterior segment cell atlas of the human eye using high throughput single-nucleus RNA sequencing (snRNAseq). We profiled 191,992 single nuclei from non-diseased anterior segment tissues from 6 human donors, identifying >60 cell types. Many are discrete, whereas others in lens and cornea form continua, corresponding to known developmental transitions that persist in adulthood. Having profiled each tissue separately, we performed an integrated analysis of the entire anterior segment revealing that some cell types are unique to single structure whereas others are shared across tissues. This integrated cell atlas was then used to investigate cell type-specific expression patterns of more than >900 human ocular disease genes identified either through Mendelian inheritance patterns or genome-wide association studies (GWAS).

2022-07-11 | GSE199013 | GEO

Intra-ocular dendritic cells characterize HLA-B27-associated acute anterior uveitis

Project description:Intra-ocular dendritic cells characterize HLA-B27-associated acute anterior uveitis

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Thyroid hormone action in human hepatocytes and the Cistromes of TRB1 and ChREBP in liver of mice

Project description:Human iPSC were differentiated to hepatocytes and treated with T3 or vehicle then total RNA was sequenced. The cistrome of TRB1 or ChREBP was delineated in liver of hypothyroid and hyperthyroid mice.

2021-11-16 | GSE133110 | GEO

Telomere Binding Protein TRB1 Preferentially Associates with Promoters of Translation Machinery genes

Project description:Background: Recently we characterised TRB1, a protein from a single-myb-histone family, as a structural and functional component of telomeres in Arabidopsis thaliana. TRB proteins, besides their ability to bind specifically telomeric DNA using their N-terminally positioned myb-like domain of the same type as in human TRF1 or TRF2 shelterin proteins, possess also histone-like domain which is involved in protein-protein interactions e.g., with POT1b. We set to investigate the genome-wide localization pattern of TRB1 to reveal its preferential mode of binding to chromatin in vivo and its potential functional roles in the genome-wide context. Results: Our results demonstrate that in addition to its roles at telomeres, TRB1 is preferentially associated with promoter regions of genes involved in ribosome biogenesis. This preference coincides with a frequent occurrence of telobox motifs in the upstream regions of genes in this category, but is not restricted to the telobox presence. Conclusions: We conclude that TRB1, in addition to its preferential telomeric localization, shows a specific genome-wide distribution pattern suggesting its role in regulation of genes involved in biogenesis of translational machinery. TRB1 DNA-binding activity investigated in 2 biological replicates (2 immunoprecipitation approaches) with controls; with technical replicates.

2015-12-21 | E-GEOD-69431 | biostudies-arrayexpress

Characterizing the TRb1 cistrome in mouse liver

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