Leptin receptor (Lepr) expressing cells in the hypothalamus regulates energy metabolism and food intake. Despite efforts to characterise their identity and function, the knowledge on cell types expressing Lepr in the adult mouse hypothalamus remains incomplete. This is in part due to low expression levels of Lepr, whic makes it difficult to identify these rare cells using single cell RNA sequencing (scRNAseq) of the whole hypothalamus. Thius we used a Lepr-ce x Rosa-lox-tdtomato mouse model to isolate Lepr+ hypothalamus cells and reveal their molecular makeup, the gene regulatory networks regulating their behaviour and response to food restriction. Here we used scanpy pipeline to analyse our scRNAseq data and identify 25 clusters of Lepr+ cells using, including previously uncharacterised Trh expression neuronal clusters. Determination of gene regulatory networks using the pyscenic pipeline reveals a role for Rfx3 in response to food restriction in Agrp neurons, which are the main responders to fasting. We further reveal the molecular makeup of Lepr cells localised to various nuclei of the adult moue hypothalamus. Our high quality dataset with ~12000 unique reads and ~4600 genes per cells provide a resource for investigating the role of Lepr hypothalamic cells as well as for studies aiming to target rare cells for gene therapy.
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