Dataset Information

Long-read isoform sequencing reveals Aroclor1260-induced isoform expression in mouse liver

ABSTRACT: Long-term exposure to polychlorinated biphenyls (PCBs) including the mixture of PCBs in Aroclor1260 (Ar1260) results in metabolic dysfunction-associated steatotic liver disease (MASLD) in mice and humans. Previously, we reported that chronic (34 wks.) exposure of normal low fat diet (LFD)-fed male mice to Ar1260 resulted in twelve hepatic RNA modifications. We confirmed the downregulation NRF2 (Nfe2l2) network pathway associated with human liver diseases. Proteomic analysis of these same liver samples identified Ar1260 exposure-associated changes in protein abundance including altered selenoproteins: GPX4 and SELENBP2 were increased and SELENOS and SELENOF were reduced. Alternative splicing (AS) has been implicated in MASLD. Here we used long-read isoform sequencing (IsoSeq) to and differential transcript usage (DTU) to specific DTU gene differences depending on the severity of liver injury with Ar1260.

ORGANISM(S): Mus musculus

PROVIDER: GSE308889 | GEO | 2026/03/03

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Hydroxylated polychlorinated biphenyls are the metabolites produced from polychlorinated biphenyls (PCBs) by drug-metabolizing enzyme cytochrome P450 1A1. These compounds are bound to transthyretin, a major plasma thyroid hormone-binding protein in amphibian tadpoles. The compounds-transthyretin complexes are transferred into the brain across the blood brain barrier in mammals. Thus these compounds are suspected to disrupt neural development in brain. We studied about the effects of hydroxylated PCBs on the thyroid system in brain using metamorphosing tadpoles of African clawed toad, Xenopus laevis. The metamorphosis assay revealed that these compounds had inhibitory effects on the thyroid hormone-induced metamorphosis. This in vivo assay was a powerful tool to detect thyroid-disrupting activities, because we were not able to detect the inhibitory effects of these compounds using thyroid hormone-responsive reporter gene assay in a cultured Xenopus cell line. A genome-wide gene expression analysis in brain following short-term exposure to these compounds demonstrated that the delay of metamorphosis and the morphological thyroid-disrupting changes could be caused partially by disruption of the thyroid hormone-induced gene expression by hydroxylated PCBs. Furthermore, we associated functional ontology terms with the transcripts whose expression were altered by thyroid hormone alone, or thyroid hormone and hydroxylated PCBs. We suggested that these approachs using a technique of bioinformatics revealed molecular mechanism of thyroid-disrupting activities in vivo. Thyroid hormones induce amphibian metamorphosis and alter a lot of thyroid hormone-responsive gene expression. We studied about the effects of hydroxylated PCBs on TH-induced gene expression. Premetamorphic tadpoles were treated with 500 nM hydroxylated PCBs in the presence of 1 nM thyroid hormone for 4 days. After exposure period total RNA was extracted from brain. Study included at least three replicate of each treatment.

Dataset Information

Long-read isoform sequencing reveals Aroclor1260-induced isoform expression in mouse liver

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets