TY - JOUR T1 - Single-cell analysis reveals cellular heterogeneity and molecular determinants of hypothalamic leptin-receptor cells JF - bioRxiv DO - 10.1101/2020.07.23.217729 SP - 2020.07.23.217729 AU - N. Kakava-Georgiadou AU - J.F. Severens AU - A.M. Jørgensen AU - I. Stoltenborg AU - K.M. Garner AU - M.C.M Luijendijk AU - V. Drkelic AU - R. van Dijk AU - S.L. Dickson AU - T.H. Pers AU - O. Basak AU - R.A.H. Adan Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/02/07/2020.07.23.217729.abstract N2 - Hypothalamic nuclei which regulate homeostatic functions express leptin receptor (LepR), the primary target of the satiety hormone leptin. Single-cell RNA sequencing (scRNA-seq) has facilitated the discovery of a variety of hypothalamic cell types. However, low abundance of LepR transcripts prevented further characterization of LepR cells. Therefore, we perform scRNA-seq on isolated LepR cells and identify eight neuronal clusters, including three uncharacterized Trh-expressing populations as well as 17 non-neuronal populations including tanycytes, oligodendrocytes and endothelial cells. Food restriction had a major impact on Agrp neurons and changed the expression of obesity-associated genes. Multiple cell clusters were enriched for GWAS signals of obesity. We further explored changes in the gene regulatory landscape of LepR cell types. We thus reveal the molecular signature of distinct populations with diverse neurochemical profiles, which will aid efforts to illuminate the multi-functional nature of leptin’s action in the hypothalamus.Competing Interest StatementThe authors have declared no competing interest. ER -