---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '21744'
abstract:
- lang: eng
text: 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.
acknowledgement: "We would like to thank Drs. Mark Andermann, Joel Geerling, and Clifford\r\nSaper,
as well as the Lowell, Tsai, and Resch laboratories for helpful discussions;\r\nAlysia
Berns, Jia Yu, and Yanfang Li for technical support; the BNORC\r\nFunctional Genomics
and Bioinformatics Core (P30DK046200) and the Iowa\r\nInstitute for Human Genetics
Genomics Division (IIHG, RRID: SCR_023422)\r\nfor helpful discussions and technical
assistance with sc/snRNA-seq; Zachary\r\nNiziolek and the Bauer Core Facility at
Harvard University, the BIDMC Flow Cytometry\r\nCore, and Heath Vignes, Michael
Shey, and Thomas Kaufman of the\r\nFlow Cytometry Facility at the University of
Iowa Carver College of Medicine\r\nfor helpful discussions and technical support;
the ICCB-Longwood Screening\r\nFacility of Harvard Medical School for assistance
with the snRNA-seq\r\nexperiments; Dr. Sayak Mitter and Vizgen support for technical
assistance\r\nwith the MERSCOPE platform; and Mara Jendro and Li-Chun (Queena) Lin\r\nfor
their assistance with MERSCOPE experiments within the Iowa\r\nNeuroBank Core in
the Iowa Neuroscience Institute at the University of Iowa\r\nCarver College of Medicine.
This research was funded by the following NIH\r\ngrants to L.T.T.: R01DK128406;
to B.B.L.: R01DK075632, R01DK134427,\r\nand 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\r\nsciences predoctoral training grant T32GM144636. Additional
funding\r\nto J.M.R. came from the American Heart Association (AHA 935362), a University\r\nof
Iowa Fraternal Order of Eagles Diabetes Research Center Pilot and\r\nFeasibility
Catalyst Grant, and an Iowa Neuroscience Institute Early Stage\r\nInvestigator award
from the Carver Trust. Y.L. was supported by a predoctoral\r\nfellowship from the
American Heart Association (AHA 25PRE1372983). A.M.D.\r\nwas supported by a postdoctoral
fellowship from the Charles A. King Trust."
article_number: '116904'
article_processing_charge: Yes
article_type: original
author:
- first_name: Yuxi
full_name: Li, Yuxi
last_name: Li
- first_name: Trevor C.
full_name: Butler, Trevor C.
last_name: Butler
- first_name: Stefano
full_name: Nardone, Stefano
last_name: Nardone
- first_name: Christopher L.
full_name: Jacobs, Christopher L.
last_name: Jacobs
- first_name: Amelia May Barnett
full_name: Douglass, Amelia May Barnett
id: de5f6fda-80fb-11ef-996f-a8c4ecd8e289
last_name: Douglass
orcid: 0000-0001-5398-6473
- first_name: Joseph C.
full_name: Madara, Joseph C.
last_name: Madara
- first_name: Miriam C.
full_name: McDonough, Miriam C.
last_name: McDonough
- first_name: Jenkang
full_name: Tao, Jenkang
last_name: Tao
- first_name: Elijah D.
full_name: Lowenstein, Elijah D.
last_name: Lowenstein
- first_name: Luhong
full_name: Wang, Luhong
last_name: Wang
- first_name: Deepti
full_name: Pant, Deepti
last_name: Pant
- first_name: Samuel J.
full_name: Walker, Samuel J.
last_name: Walker
- first_name: Annette
full_name: Wang, Annette
last_name: Wang
- first_name: Harini
full_name: Srinivasan, Harini
last_name: Srinivasan
- first_name: Zongfang
full_name: Yang, Zongfang
last_name: Yang
- first_name: John N.
full_name: Campbell, John N.
last_name: Campbell
- first_name: Linus T.
full_name: Tsai, Linus T.
last_name: Tsai
- first_name: Bradford B.
full_name: Lowell, Bradford B.
last_name: Lowell
- first_name: Jon M.
full_name: Resch, Jon M.
last_name: Resch
citation:
ama: 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
apa: 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
chicago: 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.
ieee: Y. Li et al., “A spatial and projection-based transcriptomic atlas
of paraventricular hypothalamic cell types,” Cell Reports, vol. 45, no.
2. Elsevier, 2026.
ista: 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.
mla: 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.
short: Y. Li, T.C. Butler, S. Nardone, C.L. Jacobs, A.M. Douglass, J.C. Madara,
M.C. McDonough, J. Tao, E.D. Lowenstein, L. Wang, D. Pant, S.J. Walker, A. Wang,
H. Srinivasan, Z. Yang, J.N. Campbell, L.T. Tsai, B.B. Lowell, J.M. Resch, Cell
Reports 45 (2026).
date_created: 2026-04-16T13:51:29Z
date_published: 2026-02-24T00:00:00Z
date_updated: 2026-05-04T12:00:31Z
day: '24'
ddc:
- '570'
department:
- _id: AmDo
doi: 10.1016/j.celrep.2025.116904
external_id:
pmid:
- '41581146'
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has_accepted_license: '1'
intvolume: ' 45'
issue: '2'
language:
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month: '02'
oa: 1
oa_version: Published Version
pmid: 1
publication: Cell Reports
publication_identifier:
eissn:
- 2211-1247
issn:
- 2639-1856
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: A spatial and projection-based transcriptomic atlas of paraventricular hypothalamic
cell types
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
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short: CC BY-NC-ND (4.0)
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year: '2026'
...