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

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

PROVIDER: PRJNA873741 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21204600_1.fastq.gz	Fastqsanger.gz
	SRR21204600_2.fastq.gz	Fastqsanger.gz
	SRR21204601_1.fastq.gz	Fastqsanger.gz
	SRR21204601_2.fastq.gz	Fastqsanger.gz
	SRR21204602_1.fastq.gz	Fastqsanger.gz

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Hypothalamic thyroid hormone deficiency underlies reversible anorexia in a mammalian hibernator

Project description:Mammalian hibernators survive prolonged periods of cold and resource scarcity by temporarily modulating normal physiological functions, but the mechanisms underlying these adaptations are poorly understood. The hibernation cycle of thirteen-lined ground squirrels lasts for 5–7 months and comprises weeks of hypometabolic, hypothermic torpor interspersed with 24–48-hour periods of an active-like interbout arousal (IBA) state. We show that ground squirrels, who endure the entire hibernation season without food, have negligible hunger drive during IBAs. We further demonstrate that squirrels exhibit reversible inhibition of the hypothalamic feeding center, such that hypothalamic arcuate nucleus neurons have reduced sensitivity to the orexigenic and anorexigenic effects of ghrelin and leptin, respectively. However, hypothalamic infusion of thyroid hormone during an IBA is sufficient to rescue hibernation anorexia. Our results reveal that thyroid hormone deficiency underlies hibernation anorexia and demonstrate the functional flexibility of the hypothalamic feeding center.

2024-04-03 | GSE242381 | GEO

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

Project description:Here we used single-nucleus RNA sequencing to obtain an unbiased view on the importance of TRɑ1 for hypothalamic development and cellular diversity. Sc-RNA-seq of Hypothalamus from wild type (WT) and TRɑ1R384C (TRɑ1+m) were performed.

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Hypothalamic thyroid hormone deficiency underlies reversible anorexia in a mammalian hibernator

Project description:Hypothalamic thyroid hormone deficiency underlies reversible anorexia in a mammalian hibernator

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Transgenerational effects of thyroid hormone in the hypothalamus of the F2 generation

Project description:Genetic factors do not fully account for the relatively high heritability of neurodevelopmental conditions, suggesting that non-genetic heritable factors contribute to their etiology. To evaluate the potential contribution of aberrant thyroid hormone status to the epigenetic inheritance of neurological phenotypes, we examined genetically normal mice with paternal grandparents that were developmentally overexposed to thyroid hormone due to a Dio3 mutation. Hypothalamic gene expression profiling in postnatal day 15 mice with control ancestry (Control), with a Dio3KO paternal grandmother (PGM), with Dio3KO paternal grandfather (PGF), with a heterozygous DIo3KO mother (HM) and with a heterozygous DIO3KO father (HF).

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Thyroid hormone receptor beta is required for thyrotrpin regulation and thyroid hormone production.

Project description:Thyroid hormone receptor beta is required for thyrotrpin regulation and thyroid hormone production.

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Thyroid hormone receptor alpha is required for thyroid hormone-dependent neural cell proliferation during tadpole metamorphosis

Project description:Using tadpoles mutant for thyroid hormone receptor alpha (thra), we show that TRa is required for thyroid hormone (T3) induction of cell proliferation in the brain. RNA-sequencing showed that the TRa is required for 95% of the gene regulation responses to T3.

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Project description:Thyroid hormones are important for homeostatic control of energy metabolism and body temperature. Although skeletal muscle is considered an important site for thyroid action, the contribution of thyroid hormone receptor signaling, in muscle, to whole-body energy metabolism and body temperature has not been resolved. Here, we show that thyroid hormone-induced increase in energy expenditure requires thyroid hormone receptor alpha 1 (TRa1) in skeletal muscle, but that thyroid hormone induced elevation in body temperature is independent of muscle-TRa1. In slow-twitch soleus muscle, ablation of TRa1 leads to an altered fiber type composition toward a more oxidative phenotype, which, however, does not influence running capacity or motivation to voluntary running. RNA-sequencing of soleus muscle from WT mice and TRaHSACre mice revealed differentiated transcriptional regulation of genes associated with muscle thermogenesis, such as sarcolipin and UCP3, thus providing molecular clues pertaining to the mechanistic underpinnings of TRa1-linked control of whole-body metabolic rate. Together, this work establishes a fundamental role for skeletal muscle in thyroid hormone-stimulated increase in whole-body energy expenditure.

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Target genes of thyroid hormone in cerebellum neurons

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A cardiac developmental defect prevents thyroid hormone induced tachycardia in Resistance to Thyroid Hormone alpha

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