Dataset Information

Knockout of thyroid hormone receptor alpha a (thraa) enhances cardiac regeneration in zebrafish through metabolic and hypoxic regulation

ABSTRACT: Thyroid hormone (TH) serves as a master regulator in our body, governing body metabolism and growth. Circulating TH level has been demonstrated to correlate with cardiac regenerative potential by modulating cell-cycle arrest and polyploidization in cardiomyocytes (CMs), while the molecular mechanism is still unknown. Here, we investigated the molecular mechanisms of TH signalling on heart regeneration through a time-course sequencing experiment. We disrupted the TH signalling in a zebrafish model by thyroid hormone receptor alpha a (thraa) knockout (KO). The thraa-KO zebrafish demonstrated an accelerated heart regenerative process, indicating that TH through thyroid hormone receptors (TRs) impaired heart regeneration. Our study discovered that diminished TH signalling in thraa-KO zebrafish alters the pro-inflammatory response and the regenerative process of cardiac tissue through myocardial metabolic switch. Moreover, TH signalling was shown to modulate the restoration of hypoxic response via hif3a. Altogether, our study highlighted that the role of TH signalling in modulating the progress of heart regeneration in zebrafish.

ORGANISM(S): Danio rerio

PROVIDER: GSE282482 | GEO | 2025/07/16

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Ischemic cardiopathy is the leading cause of death in the world, for which efficient regenerative therapy is not currently available. In mammals, after a myocardial infarction episode, the damaged myocardium is replaced by scar tissue featuring collagen deposition and tissue remodelling with negligible cardiomyocyte proliferation. Zebrafish, in contrast, display an extensive regenerative capacity as they are able to restore completely lost cardiac tissue after partial ventricular amputation. Due to the lack of genetic lineage tracing evidence, it is not yet clear if new cardiomyocytes arise from existing contractile cells or from an uncharacterised set of progenitors cells. Nonetheless, several genes and molecules have been shown to participate in this process, some of them being cardiomyocyte mitogens in vitro. Though questions as what are the early signals that drive the regenerative response and what is the relative role of each cardiac cell in this process still need to be answered, the zebrafish is emerging as a very valuable tool to understand heart regeneration and devise strategies that may be of potential value to treat human cardiac disease. Here, we performed a genome-wide transcriptome profile analysis focusing on the early time points of zebrafish heart regeneration and compared our results with those of previously published data. Our analyses confirmed the differential expression of several transcripts, and identified additional genes the expression of which is differentially regulated during zebrafish heart regeneration. We validated the microarray data by conventional and/or quantitative RT-PCR. For a subset of these genes, their expression pattern was analyzed by in situ hybridization and shown to be upregulated in the regenerating area of the heart. The specific role of these new transcripts during zebrafish heart regeneration was further investigated ex vivo using primary cultures of zebrafish cardiomyocytes and/or epicardial cells. Our results offer new insights into the biology of heart regeneration in the zebrafish and, together with future experiments in mammals, may be of potential interest for clinical applications. In order to study zebrafish heart regeneration, a time course experiment was realized where amputated heart regenerating were compared to control heart. Samples in triplicate were extracted at 1, 3, 5 and 7 days post-amputation.

Dataset Information

Knockout of thyroid hormone receptor alpha a (thraa) enhances cardiac regeneration in zebrafish through metabolic and hypoxic regulation

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets