RT Journal Article
SR Electronic
T1 Single-cell analysis reveals cellular heterogeneity and molecular determinants of hypothalamic leptin-receptor cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.23.217729
DO 10.1101/2020.07.23.217729
A1 N. Kakava-Georgiadou
A1 J.F. Severens
A1 A.M. Jørgensen
A1 I. Stoltenborg
A1 K.M. Garner
A1 M.C.M Luijendijk
A1 V. Drkelic
A1 R. van Dijk
A1 S.L. Dickson
A1 T.H. Pers
A1 O. Basak
A1 R.A.H. Adan
YR 2022
UL http://biorxiv.org/content/early/2022/02/07/2020.07.23.217729.abstract
AB 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.