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

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

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

Li Y, Butler TC, Nardone S, Jacobs CL, Douglass AM, Madara JC, McDonough MC, Tao J, Lowenstein ED, Wang L, Pant D, Walker SJ, Wang A, Srinivasan H, Yang Z, Campbell JN, Tsai LT, Lowell BB, Resch JM. 2026. A spatial and projection-based transcriptomic atlas of paraventricular hypothalamic cell types. Cell Reports. 45(2), 116904.

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DOI

10.1016/j.celrep.2025.116904

Journal Article | Published | English

Scopus indexed

Author

Li, Yuxi; Butler, Trevor C.; Nardone, Stefano; Jacobs, Christopher L.; Douglass, Amelia M.^ISTA ; Madara, Joseph C.; McDonough, Miriam C.; Tao, Jenkang; Lowenstein, Elijah D.; Wang, Luhong; Pant, Deepti; Walker, Samuel J.
All

Department

Douglass Group

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.

Publishing Year

2026

Date Published

2026-02-24

Journal Title

Cell Reports

Publisher

Elsevier

Acknowledgement

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.

Volume

Issue

Article Number

116904

ISSN

2639-1856

eISSN

2211-1247

IST-REx-ID

21744

Cite this

Li Y, Butler TC, Nardone S, et al. A spatial and projection-based transcriptomic atlas of paraventricular hypothalamic cell types. Cell Reports. 2026;45(2). doi:10.1016/j.celrep.2025.116904

Li, Y., Butler, T. C., Nardone, S., Jacobs, C. L., Douglass, A. M., Madara, J. C., … Resch, J. M. (2026). A spatial and projection-based transcriptomic atlas of paraventricular hypothalamic cell types. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2025.116904

Li, Yuxi, Trevor C. Butler, Stefano Nardone, Christopher L. Jacobs, Amelia M. Douglass, Joseph C. Madara, Miriam C. McDonough, et al. “A Spatial and Projection-Based Transcriptomic Atlas of Paraventricular Hypothalamic Cell Types.” Cell Reports. Elsevier, 2026. https://doi.org/10.1016/j.celrep.2025.116904.

Y. Li et al., “A spatial and projection-based transcriptomic atlas of paraventricular hypothalamic cell types,” Cell Reports, vol. 45, no. 2. Elsevier, 2026.

Li, Yuxi, et al. “A Spatial and Projection-Based Transcriptomic Atlas of Paraventricular Hypothalamic Cell Types.” Cell Reports, vol. 45, no. 2, 116904, Elsevier, 2026, doi:10.1016/j.celrep.2025.116904.

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