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

Yuxi Li; Trevor C Butler; Stefano Nardone; Christopher L Jacobs; Amelia M Douglass; Joseph C Madara; Miriam C McDonough; Jenkang Tao; Elijah D. Lowenstein; Luhong Wang; Deepti Pant; Samuel J. Walker; Annette Wang; Harini Srinivasan; Zongfang Yang; John N Campbell; Linus T Tsai; Lowell B.  Bradford; Jon M Resch

doi:10.25820/data.007554

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

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

Yuxi Li, Trevor C Butler, Stefano Nardone, Christopher L Jacobs, Amelia M Douglass, Joseph C Madara, Miriam C McDonough, Jenkang Tao, Elijah D. Lowenstein, Luhong Wang, …

University of Iowa

12/17/2025

DOI: 10.25820/data.007554

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Abstract

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.

PVH

Paraventricular hypothalamus

MERFISH

Mouse

Paraventricular nucleus of the hypothalamus

Single-cell RNA sequencing

Single-nucleus RNA sequencing

MERSCOPE

Spatial transcriptomics

Homeostasis

Pituitary

Satiety

Feeding

Sympathetic nervous system

Spinal cord

Parabrachial

Details

Title: Subtitle: A spatial and projection-based transcriptomic atlas of paraventricular hypothalamic cell types
Creators: Yuxi Li
Trevor C Butler
Stefano Nardone - Beth Israel Deaconess Medical Center
Christopher L Jacobs - Broad Institute
Amelia M Douglass - Beth Israel Deaconess Medical Center
Joseph C Madara - Beth Israel Deaconess Medical Center
Miriam C McDonough - University of Iowa
Jenkang Tao - Beth Israel Deaconess Medical Center
Elijah D. Lowenstein - Beth Israel Deaconess Medical Center
Luhong Wang - Beth Israel Deaconess Medical Center
Deepti Pant - Beth Israel Deaconess Medical Center
Samuel J. Walker - Beth Israel Deaconess Medical Center
Annette Wang - Beth Israel Deaconess Medical Center
Harini Srinivasan - Broad Institute
Zongfang Yang - Beth Israel Deaconess Medical Center
John N Campbell
Linus T Tsai - Broad Institute
Lowell B. Bradford - Beth Israel Deaconess Medical Center
Jon M Resch (Corresponding Author) - University of Iowa, Iowa Neuroscience Institute
Contributors: Brian Westra (Data Curator) - University of Iowa, Humanities and Social Sciences/Scholarly Impact
Resource Type: Dataset
DOI: 10.25820/data.007554
Publisher: University of Iowa
Grants: The role of interferon regulatory factors in tanycytes during HFD-induced inflammation, obesity and glucose dysregulation, R01DK128406, National Institute of Diabetes and Digestive and Kidney Diseases (United States, Bethesda) - NIDDK
The AgRP / POMC -> Paraventricular (PVH) -> Parabrachial (PBN) -> Limbic/Reward Satiety Circuit, R01DK075632, National Institutes of Health (United States, Bethesda) - NIH
Central Regulation of Sodium Appetite via Synergistic Action of RAAS-sensitive Neurons, R00HL144923, National Heart Lung and Blood Institute (United States, Bethesda) - NHLBI
Investigating the molecular mechanisms underlying aldosterone-mediated sodium appetite, F31HL170784, National Heart Lung and Blood Institute (United States, Bethesda) - NHLBI
Predoctoral Training in the Pharmacological Sciences, T32GM144636, National Institute of General Medical Sciences (United States, Bethesda) - NIGMS
Feedforward Activation of AgRP Neurons and Hunger, R01DK134427, National Institute of Diabetes and Digestive and Kidney Diseases (United States, Bethesda) - NIDDK
AgRP neurons: circadian control and interactions with the HPA axis, R01DK096010, National Institute of Diabetes and Digestive and Kidney Diseases (United States, Bethesda) - NIDDK
Hypothalamic regulation of blood pressure, 25PRE1372983, American Heart Association (United States, Dallas) - AHA
The basis for aldosterone-mediated activation of hindbrain NTS Hsd11b2 neurons, 935362, American Heart Association (United States, Dallas) - AHA
Grant note: Other sources of funding support: University of Iowa Fraternal Order of Eagles Diabetes Research Center Pilot and Feasibility Catalyst Grant, and a postdoctoral fellowship from the Charles A. King Trust.
Language: English
Date collected: 02/26/2024–06/12/2024
Date published: 12/17/2025
Academic Unit: Iowa Neuroscience Institute; Humanities and Social Sciences/Scholarly Impact; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
Record Identifier: 9984403060302771

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