Journal article
A spatial and projection-based transcriptomic atlas of paraventricular hypothalamic cell types
Cell reports (Cambridge), Vol.45(2), 116904
02/01/2026
DOI: 10.1016/j.celrep.2025.116904
PMID: 41581146
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.
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•Spatial transcriptomic characterization of neurons from the PVH and surrounding areas•Distinct transcriptional programs define neuroendocrine and centrally projecting PVH neurons•Projection-based snRNA-seq reveals putative PVH regulators of sympathetic drive and feeding•PVHBrs3 neurons regulate body weight and reduce feeding via projections to the parabrachial
Li et al. present a spatial transcriptomic atlas of the mouse paraventricular hypothalamus (PVH) and provide molecular markers for parabrachial- and spinal cord-projecting PVH populations. They further show that Brs3-expressing PVH neurons regulate satiety, as they co-express Mc4r, cause weight gain when silenced, and reduce food intake via parabrachial projections.
Details
- Title: Subtitle
- A spatial and projection-based transcriptomic atlas of paraventricular hypothalamic cell types
- Creators
- Yuxi Li - University of IowaTrevor C. Butler - University of IowaStefano Nardone - Beth Israel Deaconess Medical CenterChristopher L. Jacobs - Broad InstituteAmelia M. Douglass - Beth Israel Deaconess Medical CenterJoseph C. Madara - Beth Israel Deaconess Medical CenterMiriam C. McDonough - University of IowaJenkang Tao - Beth Israel Deaconess Medical CenterElijah D. Lowenstein - Beth Israel Deaconess Medical CenterLuhong Wang - Beth Israel Deaconess Medical CenterDeepti Pant - Beth Israel Deaconess Medical CenterSamuel J. Walker - Beth Israel Deaconess Medical CenterAnnette Wang - Beth Israel Deaconess Medical CenterHarini Srinivasan - Beth Israel Deaconess Medical CenterZongfang Yang - Beth Israel Deaconess Medical CenterJohn N. Campbell - University of VirginiaLinus T. Tsai - Broad InstituteBradford B. Lowell - Beth Israel Deaconess Medical CenterJon M. Resch - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.45(2), 116904
- DOI
- 10.1016/j.celrep.2025.116904
- PMID
- 41581146
- NLM abbreviation
- Cell Rep
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Publisher
- Elsevier Inc
- Grant note
- American Heart Association: AHA 25PRE1372983 University of Iowa Fraternal Order of Eagles Diabetes Research Center Pilot and Feasibility Catalyst Grant: AHA 935362 Iowa Neuroscience Institute Early Stage Investigator award from the Carver TrustCharles A. King Trust
We would like to thank Drs. Mark Andermann, Joel Geerling, and Clifford Saper, as well as the Lowell, Tsai, and Resch laboratories for helpful discussions; Alysia Berns, Jia Yu, and Yanfang Li for technical support; the BNORC Functional Genomics and Bioinformatics Core (P30DK046200) and the Iowa Institute for Human Genetics Genomics Division (IIHG, RRID: SCR_023422) for helpful discussions and technical assistance with sc/snRNA-seq; Zachary Niziolek and the Bauer Core Facility at Harvard University, the BIDMC Flow Cytometry Core, and Heath Vignes, Michael Shey, and Thomas Kaufman of the Flow Cytometry Facility at the University of Iowa Carver College of Medicine for helpful discussions and technical support; the ICCB-Longwood Screening Facility of Harvard Medical School for assistance with the snRNA-seq experiments; Dr. Sayak Mitter and Vizgen support for technical assistance with the MERSCOPE platform; and Mara Jendro and Li-Chun (Queena) Lin for their assistance with MERSCOPE experiments within the Iowa NeuroBank Core in the Iowa Neuroscience Institute at the University of Iowa Carver College of Medicine. This research was funded by the following NIH grants to L.T.T.: R01DK128406; to B.B.L.: R01DK075632, R01DK134427, and R01DK096010; to J.M.R.: R00HL144923 and R01NS141072; and to M.C.M.: F31HL170784; T.C.B. and M.C.M. were supported by a pharmacological sciences predoctoral training grant T32GM144636. Additional funding to J.M.R. came from the American Heart Association (AHA 935362) , a University of Iowa Fraternal Order of Eagles Diabetes Research Center Pilot and Feasibility Catalyst Grant, and an Iowa Neuroscience Institute Early Stage Investigator award from the Carver Trust. Y.L. was supported by a predoctoral fellowship from the American Heart Association (AHA 25PRE1372983) . A.M.D. was supported by a postdoctoral fellowship from the Charles A. King Trust.
- Language
- English
- Date published
- 02/01/2026
- Academic Unit
- Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
- Record Identifier
- 9985132203202771
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