An Atlas of Thyroid Hormone Receptors’ Target Genes in Mouse Tissues

Zekri, Yanis; Guyot, Romain; Flamant, Frédéric

doi:10.3390/ijms231911444

Cited by 30 publications

(20 citation statements)

References 43 publications

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“…We verified that the Thra AMI allele was expressed in the BAT of BATKO mice ( Figure 1B ) and that Thrb expression was drastically reduced (93%) in the BAT of BATKO mice, but not in other tissues ( Figure 1C ). As expected, the T3-induced regulation of Hr expression, a classical T3 target gene in many tissues ( Zekri et al, 2022 ), was selectively and almost completely lost in the BAT of BATKO mice ( Figure 1D ). The observed residual responses most likely reflect the presence in BAT of other cell types, like endothelial cells and immune cells ( Biagi et al, 2021 ).…”

Section: Resultssupporting

confidence: 80%

Brown adipocytes local response to thyroid hormone is required for adaptive thermogenesis in adult male mice

Zekri

Guyot

Suñer

et al. 2022

eLife

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Thyroid hormone (T3) and its nuclear receptors (TR) are important regulators of energy expenditure and adaptive thermogenesis, notably through their action in the brown adipose tissue (BAT). However, T3 acts in many other peripheral and central tissues which are also involved in energy expenditure. The general picture of how T3 regulates BAT thermogenesis is currently not fully established, notably due to the absence of extensive omics analyses and the lack of specific mice model. Here, we first used transcriptome and cistrome analyses to establish the list of T3/TR direct target genes in brown adipocytes. We then developed a novel model of transgenic mice, in which T3 signaling is specifically suppressed in brown adipocytes at adult stage. We addressed the capacity of these mice to mount a thermogenic response when challenged by either a cold exposure or a high-fat diet, and analyzed the associated changes in BAT transcriptome. We conclude that T3 plays a crucial role in the thermogenic response of the BAT, controlling the expression of genes involved in lipid and glucose metabolism and regulating BAT proliferation. The resulting picture provides an unprecedented view on the pathways by which T3 activates energy expenditure through an efficient adaptive thermogenesis in the BAT.

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Section: Resultssupporting

confidence: 80%

Brown adipocytes local response to thyroid hormone is required for adaptive thermogenesis in adult male mice

Zekri

Guyot

Suñer

et al. 2022

eLife

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“…In this subset, 251 genes were identified as only being affected at the mesor level. We validated our approach in the recently published T 3 atlas [20]. Comparing our mesor-restricted dataset (251 genes), we identified 179 DEGs that show a high overlap.…”

Section: Discussionmentioning

confidence: 93%

“…The fact that these genes are robustly rhythmic across conditions further emphasizes that sampling time should be kept consistent even in one-timepoint sampling studies (Figure 5 D; Supplementary file 5). To test the predictive efficiency of our approach, we used the published T 3 atlas that combines transcriptome and TH receptor ChipSeq data from different tissues [20]. We identified an overlap of ca.…”

Section: Resultsmentioning

confidence: 99%

Tuning of liver circadian transcriptome rhythms by thyroid hormone state in male mice

de Assis,

Harder,

Lacerda

et al. 2023

Preprint

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Thyroid hormones (THs) are important regulators of systemic energy metabolism. In the liver, they stimulate lipid and cholesterol turnover and increase systemic energy bioavailability. It is still unknown how the TH state interacts with the circadian clock, another important regulator of energy metabolism. We addressed this question using a mouse model of hypothyroidism and performed circadian analyses. Low TH levels decreased locomotor activity, food intake, and body temperature mostly in the active phase. Concurrently, liver transcriptome profiling showed only subtle effects compared to elevated TH conditions. Comparative circadian transcriptome profiling revealed alterations in mesor, amplitude, and phase of transcript levels in the livers of low-TH mice. Genes associated with cholesterol uptake, biosynthesis, and bile acid secretion showed reduced mesor. Increased and decreased cholesterol levels in the serum and liver were identified, respectively. Combining data from low- and high-TH conditions allowed the identification of 516 genes with mesor changes as molecular markers of the liver TH state. These genes participate in many known TH-associated processes. We further explored these genes and created a unique expression panel that can assess liver TH state in a time-of-day dependent manner. Our findings suggest that the liver has a low TH state under physiological conditions. Circadian profiling reveals genes as potential markers of liver TH state in one-time point studies.

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“…Most importantly, unlike several neuronal cell types, which are specific to the hypothalamus, these non-neuronal cells are found throughout the brain ( Chen et al, 2017 ), suggesting that other neuroanatomical areas might be similarly affected. Given the growing resource of genome-wide studies of T3 target genes in different tissues ( Zekri et al, 2022 ), our study provides a unique foundation to dissect the developmental from the acute actions of the hormone in brain development.…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNA-based phenotyping reveals a pivotal role of thyroid hormone receptor alpha for hypothalamic development

et al. 2023

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Thyroid hormone and its receptor TRα1 play an important role in brain development. Several animal models have been used to investigate this function, including mice heterozygous for the TRα1R384C mutation, which confers receptor-mediated hypothyroidism. These mice display abnormalities in several autonomic functions, which was partially attributed to a developmental defect in hypothalamic parvalbumin neurons. However, whether other cell types in the hypothalamus are similarly affected remains unknown. Here, we used single-nucleus RNA sequencing to obtain an unbiased view on the importance of TRα1 for hypothalamic development and cellular diversity. Our data show that defective TRα1 signaling has surprisingly little effect on the development of hypothalamic neuronal populations, but it heavily affects hypothalamic oligodendrocytes. Using selective reactivation of the mutant TRα1 during specific developmental periods, we find that early postnatal thyroid hormone action seems to be crucial for proper hypothalamic oligodendrocyte maturation. Taken together, our findings underline the well-known importance of postnatal thyroid health for brain development and provide an unbiased roadmap for the identification of cellular targets of TRα1 action in mouse hypothalamic development.

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An Atlas of Thyroid Hormone Receptors’ Target Genes in Mouse Tissues

Cited by 30 publications

References 43 publications

Brown adipocytes local response to thyroid hormone is required for adaptive thermogenesis in adult male mice

Brown adipocytes local response to thyroid hormone is required for adaptive thermogenesis in adult male mice

Tuning of liver circadian transcriptome rhythms by thyroid hormone state in male mice

Single-cell RNA-based phenotyping reveals a pivotal role of thyroid hormone receptor alpha for hypothalamic development

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