Atlas-Guided Cell-Specific Transcriptomics Identifies Pathway-Level Remodeling of Human Hypothalamic CRH Neurons in Opioid Use Disorder
- 1Louise A. Faillace, MD Department of Psychiatry and Behavioral Sciences, McGovern Medical School
Abstract
Opioid use disorder (OUD) disrupts hypothalamic stress signaling, yet the molecular state of human paraventricular nucleus (PVN) corticotropin-releasing hormone (CRH) neurons remains poorly defined. Using single-nucleus RNA sequencing of 343,819 human hypothalamic nuclei, we applied complementary human HYPOMAP/MapMyCells and mouse PVN Atlas strategies that independently converged on the standardized Allen Brain Map subcluster Splat 410 843, providing cross-atlas validation of a rare CRH-enriched PVN population. Integrated GO, Reactome and KEGG analysis revealed OUD-associated enrichment of synaptic, junctional, cytoskeletal, receptor-signaling and ion transport programs, with relative enrichment of RNA processing, ER Golgi/vesicular, endolysosomal and glycan-related functions in controls. Targeted neuropeptide analysis further identified nominal increases in OXT, GHR, GAL and PRLR and decreases in VIP, AGRP, NPY, CRHBP and CALCR. Together, these findings define a reproducible human PVN CRH population and identify coordinated pathway and neuropeptide remodeling in OUD.
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BibTeX
@misc{barrall2026atlasguided,
title = {{Atlas-Guided Cell-Specific Transcriptomics Identifies Pathway-Level Remodeling of Human Hypothalamic CRH Neurons in Opioid Use Disorder}},
author = {L. R. Barrall and P. J. Urbanczyk and B. Kluwe-Schiavon and L. Stertz and S. Rankothgedera and M. Castillo and P. H. Gunaratne and C. Walss-Bass},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.09.749970},
url = {https://www.biorxiv.org/content/10.64898/2026.09.09.749970v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Atlas-Guided Cell-Specific Transcriptomics Identifies Pathway-Level Remodeling of Human Hypothalamic CRH Neurons in Opioid Use Disorder
AU - L. R. Barrall
AU - P. J. Urbanczyk
AU - B. Kluwe-Schiavon
AU - L. Stertz
AU - S. Rankothgedera
AU - M. Castillo
AU - P. H. Gunaratne
AU - C. Walss-Bass
PY - 2026
DA - 2026/09/09
PB - bioRxiv
DO - 10.64898/2026.09.09.749970
UR - https://www.biorxiv.org/content/10.64898/2026.09.09.749970v1
AB - Opioid use disorder (OUD) disrupts hypothalamic stress signaling, yet the molecular state of human paraventricular nucleus (PVN) corticotropin-releasing hormone (CRH) neurons remains poorly defined. Using single-nucleus RNA sequencing of 343,819 human hypothalamic nuclei, we applied complementary human HYPOMAP/MapMyCells and mouse PVN Atlas strategies that independently converged on the standardized Allen Brain Map subcluster Splat 410 843, providing cross-atlas validation of a rare CRH-enriched PVN population. Integrated GO, Reactome and KEGG analysis revealed OUD-associated enrichment of synaptic, junctional, cytoskeletal, receptor-signaling and ion transport programs, with relative enrichment of RNA processing, ER Golgi/vesicular, endolysosomal and glycan-related functions in controls. Targeted neuropeptide analysis further identified nominal increases in OXT, GHR, GAL and PRLR and decreases in VIP, AGRP, NPY, CRHBP and CALCR. Together, these findings define a reproducible human PVN CRH population and identify coordinated pathway and neuropeptide remodeling in OUD.
ER -