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JUND-driven stress-responsive astrocytes promote neuronal apoptosis via enhanced gap junction signaling in autism spectrum disorder.

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The authors' code

R · 187 lines · 4.3 KB · no license

  1. #########################################################
  2. ## Olig
  4. setwd('F:/Vector/data/MouseOligo_GSE75330')
  5. library(Seurat)
  7. pbmc=readRDS('pbmc.RDS')
  9. VEC=pbmc@reductions$[email hidden]
  10. rownames(VEC)=colnames(pbmc)
  11. PCA= pbmc@reductions$[email hidden]
  13. R.PCA=apply(PCA,2,rank)
  14. RR.PCA=R.PCA/nrow(R.PCA)
  16. CUT=10
  18. MAT=matrix(0,ncol=ncol(PCA),nrow=nrow(PCA))
  19. rownames(MAT)=rownames(PCA)
  20. colnames(MAT)=colnames(PCA)
  21. MAT[which(R.PCA>nrow(PCA)-CUT | R.PCA <= CUT)]=1
  24. #########################################
  25. TAG=as.character([email hidden]$type)
  26. TAG[which(TAG=='OPC')]='OPC'
  27. TAG[which(TAG=='Differentiation-committed OPC')]='COP'
  28. TAG[which(TAG=='Newly-formed Oligodendrocytes')]='NFOL'
  29. TAG[which(TAG=='Myelin-forming Oligodendrocytes')]='MFOL'
  30. TAG[which(TAG=='Mature Oligodendrocytes')]='MOL'
  31. ################################################
  33. TMP=c()
  34. this_mat=MAT[which(TAG=='OPC'),]
  35. ratio_out=apply(this_mat, 2, sum)/nrow(this_mat)
  36. TMP=c(TMP,length(which(ratio_out>0))/ncol(PCA))
  37. #plot(ratio_out,ylim=c(0,1),type='l')
  39. this_mat=MAT[which(TAG=='COP'),]
  40. ratio_out=apply(this_mat, 2, sum)/nrow(this_mat)
  41. TMP=c(TMP,length(which(ratio_out>0))/ncol(PCA))
  42. #lines(ratio_out,type = "l",col='red')
  44. this_mat=MAT[which(TAG=='NFOL'),]
  45. ratio_out=apply(this_mat, 2, sum)/nrow(this_mat)
  46. TMP=c(TMP,length(which(ratio_out>0))/ncol(PCA))
  47. #lines(ratio_out,type = "l",col='green')
  49. this_mat=MAT[which(TAG=='MFOL'),]
  50. ratio_out=apply(this_mat, 2, sum)/nrow(this_mat)
  51. TMP=c(TMP,length(which(ratio_out>0))/ncol(PCA))
  52. #lines(ratio_out,type = "l",col='blue')
  54. this_mat=MAT[which(TAG=='MOL'),]
  55. ratio_out=apply(this_mat, 2, sum)/nrow(this_mat)
  56. TMP=c(TMP,length(which(ratio_out>0))/ncol(PCA))
  57. #lines(ratio_out,type = "l",col='gold')
  59. names(TMP)=c('OPC','COP','NFOL','MFOL','MOL')
  60. barplot(TMP,ylim=c(0,1))
  71. N.TMP=TMP
  72. N.TMP[1]=length(which(TAG=='OPC'))
  73. N.TMP[2]=length(which(TAG=='COP'))
  74. N.TMP[3]=length(which(TAG=='NFOL'))
  75. N.TMP[4]=length(which(TAG=='MFOL'))
  76. N.TMP[5]=length(which(TAG=='MOL'))
  77. barplot(N.TMP)
  89. ##########################################################
  91. # Intestine
  93. setwd('F:/Vector/data/MouseIntestine_GSE92332/')
  94. library(Seurat)
  96. pbmc=readRDS( file='pbmc.RDS')
  100. VEC=pbmc@reductions$[email hidden]
  101. rownames(VEC)=colnames(pbmc)
  102. PCA= pbmc@reductions$[email hidden]
  104. [email hidden]$type[which([email hidden]$type %in% c('Enterocyte.Immature.Distal',
  105. 'Enterocyte.Immature.Proximal') )]='EIM'
  106. [email hidden]$type[which([email hidden]$type %in% c('Enterocyte.Mature.Distal',
  107. 'Enterocyte.Mature.Proximal') )]='EM'
  108. [email hidden]$type[which([email hidden]$type %in% c('Enterocyte.Progenitor',
  109. 'Enterocyte.Progenitor.Early',
  110. 'Enterocyte.Progenitor.Late') )]='EP'
  111. [email hidden]$type[which([email hidden]$type %in% c('TA.Early',
  112. 'TA.G1','TA.G1') )]='TA'
  113. [email hidden]$type[which([email hidden]$type %in% c('Stem') )]='STEM'
  116. TAG=[email hidden]$type
  119. R.PCA=apply(PCA,2,rank)
  120. RR.PCA=R.PCA/nrow(R.PCA)
  122. CUT=10
  124. MAT=matrix(0,ncol=ncol(PCA),nrow=nrow(PCA))
  125. rownames(MAT)=rownames(PCA)
  126. colnames(MAT)=colnames(PCA)
  127. MAT[which(R.PCA> nrow(PCA)-CUT | R.PCA <= CUT)]=1
  131. TMP=c()
  132. this_mat=MAT[which(TAG=='STEM'),]
  133. ratio_out=apply(this_mat, 2, sum)/nrow(this_mat)
  134. TMP=c(TMP,length(which(ratio_out>0))/ncol(PCA))
  135. #plot(ratio_out,ylim=c(0,1),type='l')
  137. this_mat=MAT[which(TAG=='TA'),]
  138. ratio_out=apply(this_mat, 2, sum)/nrow(this_mat)
  139. TMP=c(TMP,length(which(ratio_out>0))/ncol(PCA))
  140. #lines(ratio_out,type = "l",col='red')
  142. this_mat=MAT[which(TAG=='EP'),]
  143. ratio_out=apply(this_mat, 2, sum)/nrow(this_mat)
  144. TMP=c(TMP,length(which(ratio_out>0))/ncol(PCA))
  145. #lines(ratio_out,type = "l",col='green')
  147. this_mat=MAT[which(TAG=='EIM'),]
  148. ratio_out=apply(this_mat, 2, sum)/nrow(this_mat)
  149. TMP=c(TMP,length(which(ratio_out>0))/ncol(PCA))
  150. #lines(ratio_out,type = "l",col='blue')
  152. this_mat=MAT[which(TAG=='EM'),]
  153. ratio_out=apply(this_mat, 2, sum)/nrow(this_mat)
  154. TMP=c(TMP,length(which(ratio_out>0))/ncol(PCA))
  155. #lines(ratio_out,type = "l",col='gold')
  157. names(TMP)=c('STEM','TA','EP','EIM','EM')
  158. barplot(TMP,ylim=c(0,1))
  171. N.TMP=TMP
  172. N.TMP[1]=length(which(TAG=='STEM'))
  173. N.TMP[2]=length(which(TAG=='TA'))
  174. N.TMP[3]=length(which(TAG=='EP'))
  175. N.TMP[4]=length(which(TAG=='EIM'))
  176. N.TMP[5]=length(which(TAG=='EM'))
  177. barplot(N.TMP)
  178. barplot(TMP/N.TMP)

Sup.R at commit c262ddb, no license · at the source

Overview

Authors: Qi Wang1, Huamin Yin2, Qi Jiang3, Yubo Qi1, Jieli Bai1, Zhendong Wang2, Kailai Liu1, Ruizhen Sun1, Wenhang Wang1, Canying Liu1, Weishuo Yan1, Jin Luo1, Lian Duan2, Zhiyan Shan1
ORCID iDs: Huamin Yin
  1. Department of Histology and Embryology, School of Basic Medical Sciences, Harbin Medical University,Harbin, China
  2. Central Laboratory, The First Affiliated Hospital of Wenzhou Medical University,Wenzhou, China
  3. Guangzhou National Laboratory,Guangzhou, China
Institutions: Harbin Medical University (China); First Affiliated Hospital of Wenzhou Medical University (China); Guangzhou Laboratory
Journal: Molecular autism, volume 17, issue 1, article 25
Dates: received 19 December 2025; accepted 22 April 2026; published online 19 May 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1186/s13229-026-00717-0 · PMID 42157347 · PMCID PMC13245007 · OpenAlex W7161654124
Open access: gold, a free copy (OpenAlex)
Status: code verified
Categories: genetics / omics (modality), human (organism), mouse (organism), autism (population), cellular / molecular (subfield)
Methods: Statistics, Smoothing, state filtering, decompositions
Keywords: Autism spectrum disorder, Astrocyte, Stress, JUND, Gap, Apoptosis
MeSH: Apoptosis*, Astrocytes*, Autism Spectrum Disorder*, Gap Junctions*, Neurons*, Signal Transduction*, Stress, Physiological*, Animals, Humans, Male, Mice (* major topic)
Topic: Autism Spectrum Disorder Research (Cognitive Neuroscience, Neuroscience), according to OpenAlex
Funding: National Key Research and Development Program of China (2021YFA1302500); National Natural Science Foundation of China (National Science Foundation of China) (81701350, 82271888); Natural Science Foundation of Heilongjiang Province (LH2024H022)
Citations: not cited yet (Europe PMC); 74 references in the paper

Abstract

Background: Dysregulated stress responses are increasingly implicated in the pathophysiology of autism spectrum disorder (ASD). Astrocytes, which are highly vulnerable to stress, critically support neuronal survival; however, their specific role in ASD remains poorly defined.

Methods: We analyzed single nucleus RNA sequencing data from postmortem cortices of ASD and control donors. Our analysis included enrichment analysis of astrocyte subpopulations and integrated pySCENIC-based GRN reconstruction, TF profiling, regulon-DEG analysis, and cell-cell communication. Mechanistic studies involved human iPSC-derived astrocytes-neurons co-culture and astrocyte-specific JUND overexpression in mice. Functional and behavioral assessments were performed to evaluate neuronal viability and ASD-relevant phenotypes.

Results: A subpopulation of stress-responsive astrocytes (SRAs) was identified as specifically enriched in ASD, displaying early transcriptional activation and increased abundance. These SRAs showed marked upregulation of both stress-response pathways and distinct reactive signatures. JUND was established as the core transcriptional orchestrator, controlling 23.8% of the dysregulated transcriptome that defines the core stress-responsive signature, including multiple ASD risk genes. JUND overexpression in astrocytes recapitulated the SRAs molecular profile, while astrocyte-specific JUND activation in mouse cortex elicited core ASD-like behaviors. Mechanistically, JUND upregulated the gap junction gene GJA1, enhancing astrocyte-neuron communication and promoting neuronal apoptosis. This pathogenic cascade was rescued by the gap junction inhibitor GAP27.

Limitations: This study is focused solely on specific brain regions, the generalizability of the JUND-GJA1-GAP axis across diverse ASD subtypes remains to be validated, and the complete activation pathway of JUND signaling within SRAs as well as their interaction mechanisms with other glial cells are not well understood.

Conclusions: Our findings demonstrate that a specialized astrocyte subpopulation mediates stress-induced dysfunction in ASD via a JUND-GJA1-GAP apoptotic signaling axis, providing a translational anchor for targeting astrocyte-specific pathways in ASD therapy.

Supplementary Information: The online version contains supplementary material available at 10.1186/s13229-026-00717-0.

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

Repository

Its files are read in the Code ↔ Paper reader above.

jumphone/vector

License: none: the authors keep all their rights
State: the link answers, verified on 28 September 2026
Evidence: files inventoried
Commit: c262ddbdeba9b7a94ff21ed6b80f0206078596f9, 12 January 2024
Languages: R (9)
Size: 13 files, 9 scripts
Software Heritage: not archived
Found in: the text, “Identification of astrocyte subpopulations”
Holds: README
Not found: license file, CITATION.cff, environment file, tests, continuous integration, documentation
Tools: cowplot (4 files), circlize (3 files), ComplexHeatmap (2 files), Seurat (2 files), tidyverse (2 files), igraph (1 file), limma (1 file)
Availability: 1 check, the latest on 28 September 2026: the link answers
  • 28 September 2026: the link answers
10 files
At the source: raw.githubusercontent.com/jumphone/Vector/master/Vector.R

Tracing map

Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.

What the map holds:

  • 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
  • 9 scripts, each with its path and the digest of its content;
  • no match between paragraphs and code yet;
  • neither the text of the paper nor the code itself.

Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.

Data

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All data associated with this study are present in the paper or the supplementary files.

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

Versions

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Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 14 authors, 6 keywords, 11 MeSH terms, 3 funders, 74 references.

Cite

This paper

Wang, Q., Yin, H., Jiang, Q., Qi, Y., Bai, J., Wang, Z., Liu, K., Sun, R., Wang, W., Liu, C., Yan, W., Luo, J., Duan, L., & Shan, Z. (2026). JUND-driven stress-responsive astrocytes promote neuronal apoptosis via enhanced gap junction signaling in autism spectrum disorder. Molecular autism, 17(1), 25. https://doi.org/10.1186/s13229-026-00717-0

BibTeX

@article{wang2026jund,
author = {Wang, Qi and Yin, Huamin and Jiang, Qi and Qi, Yubo and Bai, Jieli and Wang, Zhendong and Liu, Kailai and Sun, Ruizhen and Wang, Wenhang and Liu, Canying and Yan, Weishuo and Luo, Jin and Duan, Lian and Shan, Zhiyan},
title = {{JUND-driven stress-responsive astrocytes promote neuronal apoptosis via enhanced gap junction signaling in autism spectrum disorder}},
journal = {Molecular autism},
year = {2026},
month = may,
volume = {17},
number = {1},
pages = {25},
publisher = {BMC},
issn = {2040-2392},
doi = {10.1186/s13229-026-00717-0},
url = {https://doi.org/10.1186/s13229-026-00717-0},
pmid = {42157347},
pmcid = {PMC13245007}
}

RIS

TY - JOUR
AU - Wang, Qi
AU - Yin, Huamin
AU - Jiang, Qi
AU - Qi, Yubo
AU - Bai, Jieli
AU - Wang, Zhendong
AU - Liu, Kailai
AU - Sun, Ruizhen
AU - Wang, Wenhang
AU - Liu, Canying
AU - Yan, Weishuo
AU - Luo, Jin
AU - Duan, Lian
AU - Shan, Zhiyan
TI - JUND-driven stress-responsive astrocytes promote neuronal apoptosis via enhanced gap junction signaling in autism spectrum disorder
T2 - Molecular autism
J2 - Mol Autism
PY - 2026
DA - 2026/05/19
VL - 17
IS - 1
SP - 25
SN - 2040-2392
PB - BMC
DO - 10.1186/s13229-026-00717-0
UR - https://doi.org/10.1186/s13229-026-00717-0
LA - en
ER -

CSL-JSON

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