A spatial and projection-based transcriptomic atlas of paraventricular hypothalamic cell types.

Cell reports
Authors
Keywords
Abstract

The paraventricular hypothalamus (PVH) controls behavioral and physiologic processes, including appetite, social behavior, autonomic outflow, and pituitary hormone secretion. However, molecular markers for centrally projecting PVH neuron populations remain largely undefined, and a complete census of PVH cell types has not been established. Therefore, we performed extensive single-cell/nucleus RNA sequencing to catalog PVH neuron subtypes and multiplexed error-robust fluorescence in situ hybridization (MERFISH) to map them spatially. Our spatial transcriptomic atlas resolves 26 Sim1 and 29 GABAergic neuron populations from the PVH and surrounding areas. Additionally, projection-based profiling identified neurons that project to the parabrachial region (PB) and spinal cord, helping to determine PVH populations that regulate satiety and sympathetic nervous system activity, respectively. Notably, activation of PB-projecting PVH neurons expressing Brs3 reduces food intake, and silencing them causes obesity. Together, this atlas contributes high-resolution PVH spatial and circuit-based gene expression profiles, representing a valuable resource for the field of homeostasis.

Year of Publication
2026
Journal
Cell reports
Volume
45
Issue
2
Pages
116904
Date Published
01/2026
ISSN
2211-1247
DOI
10.1016/j.celrep.2025.116904
PubMed ID
41581146
Links