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RNA-sequencing reveals predominance of THRA splicing isoform 2 in developing human brain [treated]

ABSTRACT: Thyroid Hormone Receptor α (THRα) is a nuclear hormone receptor for triiodothyronine (T3) that acts as a transcription factor. Depending on its splicing pattern, it may act either as a stimulator or inhibitor of gene transcription. The relative proportions of the THRα splicing isoforms (THRα1 versus THRα2) in different tissues are crucial for the outcome of transcription regulation. To date, the tissue-specific expression patterns of the two main isoforms in human cortical development have not been determined. To address this gap, we generated cortical brain organoids in vitro following the STEMdiff™ Cerebral Organoid Kit guidelines. Samples were treated with 50nM T3 48h before collection to perturb the Thyroid Hormone-regulated system. We then generated the stranded bulk RNA-Seq dataset here presented. We employed a bioinformatics pipeline to ensure the quality of the dataset and to extract and quantify the read counts specific for our isoforms of interest. We observed a steady increase of THRα transcript in time and a strong predominance of THRα2 transcripts at all stages.

ORGANISM(S): Homo sapiens

PROVIDER: GSE250143 | GEO | 2024/09/12

REPOSITORIES: GEO

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RNA-sequencing reveals predominance of THRA splicing isoform 2 in developing human brain [untreated]

Project description:Thyroid Hormone Receptor α (THRα) is a nuclear hormone receptor for triiodothyronine (T3) that acts as a transcription factor. Depending on its splicing pattern, it may act either as a stimulator or inhibitor of gene transcription. The relative proportions of the THRα splicing isoforms (THRα1 versus THRα2) in different tissues are crucial for the outcome of transcription regulation. To date, the tissue-specific expression patterns of the two main isoforms in human cortical development have not been determined. To address this gap, we generated cortical brain organoids in vitro following the STEMdiff™ Cerebral Organoid Kit guidelines. We then generated the stranded bulk RNA-Seq dataset here presented. We employed a bioinformatics pipeline to ensure the quality of the dataset and to extract and quantify the read counts specific for our isoforms of interest. We observed a steady increase of THRα transcript in time and a strong predominance of THRα2 transcripts at all stages.

2024-09-12 | GSE250142 | GEO

RNA-sequencing reveals strong predominance of THRA splicing isoform 2 in the developing and adult human brain

Project description:Thyroid hormone receptor alpha (THRα) is a nuclear hormone receptor that binds triiodothyronine (T3) and acts as an important transcription factor in development, metabolism and reproduction. THRα has in mammals two major splicing isoforms, THRα1 and THRα2. The better characterized isoform, THRα1, is a transcriptional stimulator of genes involved in cell metabolism and growth. The less well characterized isoform, THRα2, lacks the Ligand Binding Domain (LBD) and is thought to act as an inhibitor of THRα1 action. The ratio of THRα1 to THRα2 splicing isoforms is therefore critical for transcriptional regulation in different tissues and during development. However, the expression patterns of both isoforms have not been studied in healthy human tissues or in the developing brain. Given the lack of commercially available isoform-specific antibodies, we addressed this question by analyzing four bulk RNA-sequencing datasets and two scRNA-sequencing datasets to determine the RNA expression levels of human THRA1 and THRA2 transcripts in healthy adult tissues and in the developing brain. We demonstrate how 10X Chromium scRNA-seq datasets can be used to perform splicing-sensitive analyses of isoforms that differ at the 3'-end. In all datasets, we discovered a strong predominance of THRA2 transcripts at all stages of brain development and in central nervous system from healthy human adults.

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Isoform-specific transcriptional activity of overlapping targets that respond to thyroid hormone receptors a1 and b1

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2022-04-04 | PXD030403 | Pride

Expression data from mouse liver over-expressing either GFP alone or biotinylated-TRb1 and GFP

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