Published 2025 | Version v1
Dataset Open

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

Authors/Creators

  • 1. Department of Neuroscience and Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
  • 2. Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
  • 3. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
  • 4. Department of Biology, University of Virginia, Charlottesville, Virginia, USA
  • 5. Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA
  • 6. Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa, USA
  • 7. Fraternal Order of Eagles Diabetes Research Center, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

Description

The paraventricular hypothalamus (PVH) controls many behavioral and physiologic processes, including appetite, social behavior, autonomic outflow, and pituitary hormone secretion. However, molecular markers for functionally-specific PVH neuron projections 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 identify unique neuronal subtypes and multiplexed error-robust fluorescence in situ hybridization (MERFISH) to validate and map them spatially. Our spatial transcriptomic atlas resolved 26 Sim1+ and 29 GABAergic neuron populations from the PVH and surrounding areas, revealing multiple subtypes not described previously and distinct transcriptional programs between neuroendocrine and centrally-projecting neurons. Additionally, projection-based profiling determined neuronal subtypes that project to the parabrachial region (PB) and spinal cord, helping to identify PVH populations that regulate satiety and sympathetic nervous system activity, respectively. Notably, PB-projecting PVH neurons expressing bombesin-like receptor 3 (Brs3) induce satiety, and their silencing causes obesity. Together, this atlas fills a critical gap by contributing high-resolution PVH spatial and circuit-based gene expression profiles, representing a valuable resource for the field of homeostasis.

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