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Single-nucleus RNA-seq of mouse arcuate nucleus of the hypothalamus after DOCA-salt treatment

ABSTRACT: Single-nucleus RNA-seq of mouse arcuate nucleus of the hypothalamus after DOCA-salt treatment

PROVIDER: PRJNA913972 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22821534_1.fastq.gz	Fastqsanger.gz
	SRR22821534_2.fastq.gz	Fastqsanger.gz
	SRR22821535_1.fastq.gz	Fastqsanger.gz
	SRR22821535_2.fastq.gz	Fastqsanger.gz
	SRR22821536_1.fastq.gz	Fastqsanger.gz

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Single-nucleus RNA-seq of mouse arcuate nucleus of the hypothalamus after DOCA-salt treatment

Project description:We compared the transcriptomic changes in cell populations of the arcuate nucleus of the hypothalamus in 21 day treated DOCA-salt male mice versus sham male mice using high-throughput single-nucleus RNA-seq.

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Single-cell gene expression profile of the postnatal mouse arcuate nucleus in the hypothalamus

Project description:m6A, the most prevalent internal modification on mRNAs, plays important roles in the nervous system. Whether neurogenesis in the hypothalamus, a region critical for controlling appetite, is regulated by m6A signaling, especially in humans, remains unclear. Here we showed that deletion of m6A writer Mettl14 in the mouse embryonic hypothalamus led to adult obesity, with impaired glucose-insulin homoeostasis and increased energy intake. Mechanistically, deletion of Mettl14 leads to hypothalamic arcuate nucleus neurogenesis deficits with reduced generation of feeding-related neurons and dysregulation of neurogenesis-related m6A-tagged transcripts. Deletion of m6A writer Mettl3, or m6A reader Ythdc1, shared similar phenotypes. METTL14 or YTHDC1 knockdown also led to reduced generation of feeding-related neurons in human brain subregion-specific arcuate nucleus organoids. Our studies reveal a conserved role of m6A signaling in arcuate nucleus neurogenesis in mice and human organoids and shed light on the developmental basis of epitranscriptomic regulation of food intake and energy homeostasis.

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Arcuate nucleus of the hypothalamus cells are sensitive to nutritional state in a sex dependent manner.

Project description:Obesity has reached epidemic levels and obesity increases the risk for negative health outcomes including type 2 diabetes. Sex differences are evident in metabolic homeostasis with differences seen both in amount and location of adipose stores. Males store more adipose viscerally whereas females store adipose subcutaneously. Interestingly, this can be affected by the brain. The arcuate nucleus of the hypothalamus is a key brain region that exerts control over feeding behavior and metabolism. The cells of the arcuate are heterogeneous in their transcriptomic expression and in their functions. Here we perform single nuclei RNA-sequencing of the arcuate in females and males under varying nutritional states. We found that Agrp neurons were the most sensitive to nutritional state and this was more pronounced in females than in males. KNDy neurons were also sensitive to nutritional state and major sex differences were observed. Dopamine neurons of the arcuate had major sex differences. Ghrh neurons saw moderate nutritional regulation and sexual dimorphism. Both microglia and oligodendrocytes had moderate differences observed between nutritional states. This study represents the first major effort to characterize sex differences across nutritional states in the arcuate.

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