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Transcriptomic landscape of microglia in mouse models of social dysfunction and oxytocin-mediated recovery.

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  1. Transcriptomic Landscape of Microglia in Mouse Models of Social Dysfunction and Oxytocin-Mediated Recovery

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Overview

Authors: Masafumi Tsurutani1,2, Haruaki Sato1, Mitsue Hagihara1, Dooseon Cho3, Mitsutaka Kadota3, Takefumi Kondo3, Kazunari Miyamichi1,4
ORCID iDs: Kazunari Miyamichi
  1. Laboratory for Comparative Connectomics, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo 650-0047, Japan
  2. Graduate School of Biostudies, Kyoto University, Kyoto, Kyoto 606-8501, Japan
  3. Laboratory for Developmental Genome System, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo 650-0047, Japan
  4. CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan
Institutions: Kyoto University (Japan); National Center of Neurology and Psychiatry (Japan); RIKEN Center for Biosystems Dynamics Research (Japan); Japan Science and Technology Agency (Japan)
Journal: iScience, volume 29, issue 9, article 117412
Dates: received 26 February 2026; accepted 17 August 2026; published online 2 September 2026
Type: Research article · Language: English
License: CC BY-NC
Identifiers: DOI 10.1016/j.isci.2026.117412 · PMID 42733638 · PMCID PMC13571280 · OpenAlex W7132829496
Open access: gold, a free copy (OpenAlex)
Preprint: doi:10.64898/2026.02.26.708356
Status: empty repository
Categories: genetics / omics (modality), mouse (organism), autism (population), cellular / molecular (subfield)
Methods: Smoothing, state filtering, decompositions, fMRI & imaging
Keywords: autism spectrum disorder, oxytocin neurons, microglia, spatial transcriptomics, single-cell transcriptomics
Topic: Neuroendocrine regulation and behavior (Social Psychology, Psychology), according to OpenAlex
Funding: Takeda Science Foundation; Japan Society for the Promotion of Science (JPMJCR2021, CREST, 25K02368); National Bioscience Database Center (JPMJCR2021); RIKEN (JPMJCR2021); RIKEN Center for Biosystems Dynamics Research; Centre de Recherche en Économie et Statistique
Citations: not cited yet (Europe PMC); 46 references in the paper
Research resources: Goat anti-mCherry RRID:AB_2333093, Donkey anti-chicken IgY, Alexa Fluor 647 RRID:AB_2337392, Donkey anti-rabbit IgG, Alexa Fluor 647 RRID:AB_2536183, Donkey anti-rabbit IgG, Alexa Fluor 488 RRID:AB_2762833, RRID:AB_2762839, Chicken anti-IBA1 RRID:AB_2891282, RRID:AB_514500, Rabbit anti-OT RRID:AB_572258, R RRID:SCR_001905, Python Programming Language RRID:SCR_008394, Illustrator CC RRID:SCR_010279, Seurat RRID:SCR_016341, clusterProfiler RRID:SCR_016884, Napari RRID:SCR_022765, decoupleR RRID:SCR_027127

Abstract

Atypical sociability is a hallmark of neurodevelopmental disorders arising from genetic susceptibility and prenatal environmental perturbations that can affect diverse brain cell types. Using single-cell transcriptomics, we previously identified selective vulnerability of parvocellular oxytocin (OT) neurons in the paraventricular hypothalamus (PVH) following embryonic exposure to valproic acid (VPA), a teratogen that induces social deficits. Neonatal chemogenetic activation of OT neurons rescued these behavioral abnormalities and partially restored dysregulated gene expression. However, the effects of VPA exposure and OT neuron stimulation on non-neuronal PVH cells remained unclear. Here, we show that VPA induces transcriptional abnormalities in PVH microglia. Spatial transcriptomics revealed altered distributions of PVH microglial subtypes. Notably, neonatal OT neuron stimulation reversed a subset of VPA-induced microglial gene downregulation, while pharmacological manipulation of microglia normalized aberrant OT gene expression in putative parvocellular OT neurons. These findings support bidirectional OT neuron-microglia interactions that may underlie social dysfunction following embryonic VPA exposure.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Repository

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MasaTsurutani/Transcriptomic-Landscape-of-Microglia-in-Mouse-Models-of-Social-Dysfunction-and-Oxytocin-Mediated

License: none: the authors keep all their rights
State: the link answers, verified on 26 September 2026
Evidence: files inventoried
Commit: dff4054bc7728a9153116472045cbe57e5815411, 5 August 2026
Size: 3 files, 0 scripts
Software Heritage: not archived
Found in: “Data and code availability”
Holds: README
Not found: license file, CITATION.cff, environment file, tests, continuous integration, documentation
Availability: 1 check, the latest on 26 September 2026: the link answers
  • 26 September 2026: the link answers
1 file
At the source: github.com/MasaTsurutani/Transcriptomic-Landscape-of-Microglia-in-Mouse-Models-of-Social-Dysfunction-and-Oxytocin-Mediated

The paper's code and data availability statement is in the Data section.

Tracing map

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Data

Datasets cited

Data and code availability

Xenium data generated in this study have been deposited in the GEO repository (GSE318415 (https://ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318415)). All data supporting the conclusions of this work are included in the main and supplementary figures.

This study does not report newly developed code. All Python and R scripts used for data analysis have been deposited at https://github.com/MasaTsurutani/Transcriptomic-Landscape-of-Microglia-in-Mouse-Models-of-Social-Dysfunction-and-Oxytocin-Mediated.

Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Versions

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Version 3, 28 September 2026

  • Authors: added Kazunari Miyamichi (0000-0002-7807-8436); removed Kazunari Miyamichi
  • Funding: added Takeda Science Foundation; Japan Society for the Promotion of Science: JPMJCR2021, CREST, 25K02368; Japan Science and Technology Agency: JPMJCR2021; RIKEN: JPMJCR2021; RIKEN Center for Biosystems Dynamics Research; Centre de Recherche en Économie et Statistique

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 7 authors, 5 keywords, 46 references, 15 RRIDs.

Cite

This paper

Tsurutani, M., Sato, H., Hagihara, M., Cho, D., Kadota, M., Kondo, T., & Miyamichi, K. (2026). Transcriptomic landscape of microglia in mouse models of social dysfunction and oxytocin-mediated recovery. iScience, 29(9), 117412. https://doi.org/10.1016/j.isci.2026.117412

BibTeX

@article{tsurutani2026transcriptomic,
author = {Tsurutani, Masafumi and Sato, Haruaki and Hagihara, Mitsue and Cho, Dooseon and Kadota, Mitsutaka and Kondo, Takefumi and Miyamichi, Kazunari},
title = {{Transcriptomic landscape of microglia in mouse models of social dysfunction and oxytocin-mediated recovery}},
journal = {iScience},
year = {2026},
month = sep,
volume = {29},
number = {9},
pages = {117412},
publisher = {Elsevier},
issn = {2589-0042},
doi = {10.1016/j.isci.2026.117412},
url = {https://doi.org/10.1016/j.isci.2026.117412},
pmid = {42733638},
pmcid = {PMC13571280}
}

RIS

TY - JOUR
AU - Tsurutani, Masafumi
AU - Sato, Haruaki
AU - Hagihara, Mitsue
AU - Cho, Dooseon
AU - Kadota, Mitsutaka
AU - Kondo, Takefumi
AU - Miyamichi, Kazunari
TI - Transcriptomic landscape of microglia in mouse models of social dysfunction and oxytocin-mediated recovery
T2 - iScience
J2 - iScience
PY - 2026
DA - 2026/09/02
VL - 29
IS - 9
SP - 117412
SN - 2589-0042
PB - Elsevier
DO - 10.1016/j.isci.2026.117412
UR - https://doi.org/10.1016/j.isci.2026.117412
LA - en
ER -

CSL-JSON

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