OSCR

Amygdala astrocyte primary cilium mechanisms contribute to stress behaviours.

Code ↔ Paper

The paper beside its authors' code: matches between them have not been computed for this paper yet.

Paper

Loaded from Europe PMC by your browser, not stored by OSCR: doi.org · Europe PMC

The paper is loaded when this pane is shown.

The authors' code

R · 57 lines · 2.6 KB · other

  1. ## Create data for boxplots of all intersections
  2. IntersectionBoxPlot <- function(data1, data2, start_col, names){
  3. end_col <- ((start_col + length(names)) - 1)
  4. data2 <- data2[which(rowSums(data2[ ,start_col:end_col]) != 0), ]
  5. #tagging because x axis values need to be 1:number of sets so they line up with their intersections
  6. data2$tag <- 1:nrow(data2)
  7. sets <- list()
  8. intersections <- list()
  9. box_plot_data <- data.frame()
  10. for(i in 1:nrow(data1)){
  11. sets[[i]] <- colnames(data1)[which(data1[i, 1:length(names)] == 0)]
  12. }
  13. for(i in 1:length(sets)){
  14. intersections[[i]] <- data2[(rowSums(data2[ ,start_col:end_col]) == (length(names) - length(as.character(sets[[i]])))), ]
  15. intersections[[i]] <- Wanted(intersections[[i]], as.character(sets[[i]]))
  16. end <- ((start_col + (length(names) - length(as.character(sets[[i]]))))-1)
  17. if(start_col == end){
  18. intersections[[i]] <- intersections[[i]][(intersections[[i]][ ,start_col]) == 1, ]
  19. intersections[[i]] <- intersections[[i]]$tag
  20. }
  21. else{
  22. num <- length(names) - length(as.character(sets[[i]]))
  23. intersections[[i]] <- intersections[[i]][(rowSums(intersections[[i]][ ,start_col:end]) == num), ]
  24. intersections[[i]] <- intersections[[i]]$tag
  25. }
  26. intersections[[i]] <- data2[data2$tag %in% as.numeric(intersections[[i]]), ]
  27. intersections[[i]]$x <- i
  28. }
  29. for(i in 1:length(intersections)){
  30. box_plot_data <- rbind(box_plot_data, intersections[[i]])
  31. }
  32. return(box_plot_data)
  33. }
  35. ## Generate boxplot summary plots
  36. BoxPlotsPlot <- function(bdat, att, att_color){
  37. yaxis <- as.character(att)
  38. col <- match(att, colnames(bdat))
  39. colnames(bdat)[col] <- "attribute"
  40. upper_xlim <- as.numeric((max(bdat$x) + 1))
  41. plot_lims <- as.numeric(0:upper_xlim)
  42. bdat$x <- as.factor(bdat$x)
  43. boxplots <- ggplotGrob(ggplot()
  44. + theme_bw() +ylab(yaxis)
  45. + scale_x_discrete(limits = plot_lims, expand = c(0,0))
  46. + theme(plot.margin = unit(c(-0.7,0,0,0), "cm"),
  47. axis.title.y = element_text(vjust = -0.8),
  48. axis.ticks.x = element_blank(),
  49. axis.text.x = element_blank(),
  50. panel.border = element_blank(),
  51. panel.grid.minor = element_blank(),
  52. panel.grid.major = element_blank(),
  53. axis.title.x = element_blank())
  54. + geom_boxplot(data = bdat, aes_string(x="x", y="attribute"),
  55. fill = att_color, colour = "gray80"))
  56. return(boxplots)
  57. }

Boxplot.R at commit d2dd1d9, under other · at the source

Overview

Authors: Sara G Pelaz1, Katsukuni Mitsui1,2, Natalia Kolosowska3,4, Haley Fritch5, Chiranjivi Neupane1, Vanessa H Casha1, Marta Alonso-Gardón1, Vijaya Pandey6, Lizheng Wang7, Riki Kawaguchi8,9, James A Wohlschlegel6, Jiami Guo7, Steven A McCarroll5,10, Sabina Berretta3,4,5, Baljit S Khakh1,11,12
ORCID iDs: Sara G Pelaz, Katsukuni Mitsui, Haley Fritch, Chiranjivi Neupane, Vanessa H Casha, Vijaya Pandey, James A Wohlschlegel, Jiami Guo, Steven A McCarroll, Sabina Berretta, Baljit S Khakh
  1. Department of Physiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA USA
  2. Research Center of Neurology, ONO Pharmaceutical, Osaka, Japan
  3. McLean Hospital, Belmont, MA USA
  4. Department of Psychiatry, Program in Neuroscience, Harvard Medical School, Boston, MA USA
  5. Broad Institute of MIT and Harvard, Cambridge, MA USA
  6. Department of Biological Chemistry, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA USA
  7. Department of Cell Biology and Anatomy, Alberta Children’s Hospital Research Institute, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta Canada
  8. Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA USA
  9. Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA USA
  10. Howard Hughes Medical Institute and Harvard Medical School Department of Genetics, Boston, MA USA
  11. Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA USA
  12. UK Dementia Research Institute, Cardiff University, Cardiff, UK
Institutions: University of California, Los Angeles (United States); Ono Pharmaceutical (Japan) (Japan); Harvard University (United States); McLean Hospital (United States); Broad Institute (United States); University of Calgary (Canada); Alberta Children's Hospital Research Institute; Hotchkiss Brain Institute (Canada); Howard Hughes Medical Institute (United States); UK Dementia Research Institute (United Kingdom); Cardiff University (United Kingdom)
Journal: Nature, volume 657, issue 8131, pages 455-468
Dates: received 21 July 2025; accepted 1 July 2026; published online 5 August 2026; in print 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41586-026-10874-0 · PMID 42557328 · PMCID PMC13558064 · OpenAlex W7172540636
Open access: hybrid, a free copy (OpenAlex)
Status: code verified
Categories: human (organism), mouse (organism), depression (population), cellular / molecular (subfield)
Methods: Statistics, Evoked potentials, fMRI & imaging, Single-unit activity, calcium imaging
Keywords: Astrocyte, Depression, Cellular neuroscience, Molecular neuroscience
MeSH: Amygdala*, Astrocytes*, Cilia*, Stress, Psychological*, Animals, Female, Humans, Male, Mice, Receptors, G-Protein-Coupled, Receptors, Lysosphingolipid, Signal Transduction, Sphingosine-1-Phosphate Receptors (* major topic)
Topic: Genetic and Kidney Cyst Diseases (Genetics, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Citations: not cited yet (Europe PMC); 105 references in the paper

Abstract

Understanding how adverse life events trigger stress-related behavioural changes remains an unresolved challenge. The amygdala is integral to emotion and stress responses1 and comprises astrocytes, neurons and other cells. Here we show that amygdala astrocytes contribute to stress-related behaviours through signalling mechanisms related to their primary cilia2. Amygdala astrocytes are altered during stress at the protein and gene expression level, display reduced expression of molecules related to primary cilia3,4 and have morphologically short primary cilia5,6. G protein-coupled receptors (GPCRs) are central to astrocyte7 and primary cilia2,8,9 function. Therefore, we speculated that GPCR signalling activation might be beneficial in stress-related behavioural disorders. We identified amygdala astrocyte GPCRs as regulators of responses following stress. Chemogenetics and targeting of native sphingosine-1-phosphate receptor 1 (S1PR1) GPCRs led to the restoration of astrocyte primary cilia length, corrected molecular alterations and improved stress-related behaviours. Cilium-related genes were abundantly expressed in human amygdala astrocytes, with many displaying disrupted expression in stress-related brain disorders. S1PR1 was also highly expressed in amygdala astrocytes from human tissue. Selective genetic disruption of amygdala astrocyte primary cilia in mice altered some stress-related behaviours and gene expression of astrocytes and parenchymal cells. These data confirm that astrocytic cilia have important roles in this brain nucleus. In summary, amygdala astrocytes and their primary cilia are disrupted during stress, and their restoration is accompanied by stress-related molecular and behavioural improvements. Astrocyte primary cilia-related mechanisms may therefore provide new treatment strategies for stress-related and other brain disorders.

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

Repository

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

hms-dbmi/UpSetR

License: other
State: the link answers, verified on 27 September 2026
Evidence: files inventoried
Commit: d2dd1d9e9ffc2b3bc47509467f89f37aefe7cb93, 20 May 2026
Languages: R (29)
Size: 51 files, 29 scripts
Software Heritage: not archived
Found in: “Code availability”
Holds: README, license file, environment (DESCRIPTION), continuous integration, documentation, 4 notebooks
Not found: CITATION.cff, tests
Tools: ggplot2 (3 files)
Availability: 1 check, the latest on 27 September 2026: the link answers
  • 27 September 2026: the link answers
31 files
At the source: github.com/hms-dbmi/UpSetR

Code availability

For RNA-seq, differential gene expression and enrichment analysis used the R package limma-voom to process RNA counts (v.3.60; https://rdrr.io/bioc/limma/man/voom.html) and batch correction and removal of unwanted variation was done with RUVr101. scRNA-seq data were analysed using Seurat (https://CRAN.R-project.org/package=Seurat (https://urldefense.com/v3/__https:/cran.r-project.org/package=Seurat__;!!F9wkZZsI-LA!GRJeGOVwCVKraw6z9FctQApuboM7TEqz-FAD4o_EPZrFhXzIZmCoatkYCx4YPIUpaZOkeDZp6FhRxhAn8OovMWMiGZg$)). Visualization of set intersections was done with UpSetR (v.1.4.0; https://github.com/hms-dbmi/UpSetR). For proteomics, label-free quantification was carried out using DIA-NN (v.1.8.1). Principal component data visualization was conducted with the R package DESeq2 (v.1.44.0; https://bioconductor.org/packages/release/bioc/html/DESeq2.html). Differential protein expression and enrichment analysis was conducted using limma (v.3.60; https://bioconductor.org/packages/release/bioc/html/limma.html). For calcium imaging, data were analysed in R using GECIquant (v.1.0), pracma (v1.9.9; https://cran.r-project.org/web/packages/pracma/index.html) and DescTools (v.0.99.55; https://cran.r-project.org/web/packages/DescTools/index.html).

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

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;
  • 29 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

Datasets cited

Data availability

All new astrocyte RNA-seq data generated in this study have been deposited into the Gene Expression Omnibus with accession identifier GSE285150 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE285150). Previously published data for the 13 regions of the brain can be found with the accession identifier GSE198024 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE198024). All new astrocyte proteomic data generated in this study have been deposited into the MassIVE repository and can be accessed using the identifier MSV000096647 (https://massive.ucsd.edu/ProteoSAFe/QueryMSV?id=MSV000096647). Lists of DEGs, hits and DEPs for all experiments can be found in the Supplementary Information. Source data are provided with this paper.

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

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 3, 28 September 2026

  • Publisher: n/a → Nature Portfolio

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 15 authors, 4 keywords, 13 MeSH terms, 104 references.

Cite

This paper

Pelaz, S. G., Mitsui, K., Kolosowska, N., Fritch, H., Neupane, C., Casha, V. H., Alonso-Gardón, M., Pandey, V., Wang, L., Kawaguchi, R., Wohlschlegel, J. A., Guo, J., McCarroll, S. A., Berretta, S., & Khakh, B. S. (2026). Amygdala astrocyte primary cilium mechanisms contribute to stress behaviours. Nature, 657(8131), 455-468. https://doi.org/10.1038/s41586-026-10874-0

BibTeX

@article{pelaz2026amygdala,
author = {Pelaz, Sara G and Mitsui, Katsukuni and Kolosowska, Natalia and Fritch, Haley and Neupane, Chiranjivi and Casha, Vanessa H and Alonso-Gardón, Marta and Pandey, Vijaya and Wang, Lizheng and Kawaguchi, Riki and Wohlschlegel, James A and Guo, Jiami and McCarroll, Steven A and Berretta, Sabina and Khakh, Baljit S},
title = {{Amygdala astrocyte primary cilium mechanisms contribute to stress behaviours}},
journal = {Nature},
year = {2026},
month = aug,
volume = {657},
number = {8131},
pages = {455--468},
publisher = {Nature Portfolio},
issn = {0028-0836},
doi = {10.1038/s41586-026-10874-0},
url = {https://doi.org/10.1038/s41586-026-10874-0},
pmid = {42557328},
pmcid = {PMC13558064}
}

RIS

TY - JOUR
AU - Pelaz, Sara G
AU - Mitsui, Katsukuni
AU - Kolosowska, Natalia
AU - Fritch, Haley
AU - Neupane, Chiranjivi
AU - Casha, Vanessa H
AU - Alonso-Gardón, Marta
AU - Pandey, Vijaya
AU - Wang, Lizheng
AU - Kawaguchi, Riki
AU - Wohlschlegel, James A
AU - Guo, Jiami
AU - McCarroll, Steven A
AU - Berretta, Sabina
AU - Khakh, Baljit S
TI - Amygdala astrocyte primary cilium mechanisms contribute to stress behaviours
T2 - Nature
J2 - Nature
PY - 2026
DA - 2026/08/05
VL - 657
IS - 8131
SP - 455
EP - 468
SN - 0028-0836
PB - Nature Portfolio
DO - 10.1038/s41586-026-10874-0
UR - https://doi.org/10.1038/s41586-026-10874-0
LA - en
ER -

CSL-JSON

{
"id": "10.1038/s41586-026-10874-0",
"type": "article-journal",
"title": "Amygdala astrocyte primary cilium mechanisms contribute to stress behaviours",
"container-title": "Nature",
"author": [
{
"family": "Pelaz",
"given": "Sara G"
},
{
"family": "Mitsui",
"given": "Katsukuni"
},
{
"family": "Kolosowska",
"given": "Natalia"
},
{
"family": "Fritch",
"given": "Haley"
},
{
"family": "Neupane",
"given": "Chiranjivi"
},
{
"family": "Casha",
"given": "Vanessa H"
},
{
"family": "Alonso-Gardón",
"given": "Marta"
},
{
"family": "Pandey",
"given": "Vijaya"
},
{
"family": "Wang",
"given": "Lizheng"
},
{
"family": "Kawaguchi",
"given": "Riki"
},
{
"family": "Wohlschlegel",
"given": "James A"
},
{
"family": "Guo",
"given": "Jiami"
},
{
"family": "McCarroll",
"given": "Steven A"
},
{
"family": "Berretta",
"given": "Sabina"
},
{
"family": "Khakh",
"given": "Baljit S"
}
],
"container-title-short": "Nature",
"volume": "657",
"issue": "8131",
"page": "455-468",
"DOI": "10.1038/s41586-026-10874-0",
"PMID": "42557328",
"PMCID": "PMC13558064",
"ISSN": "0028-0836",
"publisher": "Nature Portfolio",
"URL": "https://doi.org/10.1038/s41586-026-10874-0",
"language": "en",
"issued": {
"date-parts": [
[
2026,
8,
5
]
]
}
}

The tracing map gets a citation of its own once an author has validated it and it has a DOI.

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1126/sciadv.aed5548 [code]
In situ proteomics unveils specialized domains for extrasynaptic signaling on neuronal cilia.
Journal: Science advances
In common: mouse, cellular / molecular, 7 references
[2] doi:10.1038/s41593-026-02354-5 [code]
Focal astrocyte loss reveals nuclear translocation during lesion repopulation.
Journal: Nature neuroscience
In common: ggplot2, mouse, cellular / molecular, 4 references
[3] doi:10.1038/s41467-026-76132-z [code]
ATP13A4 gates extracellular polyamine levels to control excitatory synaptogenesis.
Journal: Nature communications
In common: ggplot2, mouse, 4 references
[4] doi:10.7554/elife.93640 [code]
Sibling chimerism among microglia in marmosets.
Journal: eLife
In common: ggplot2, cellular / molecular, author Steven A McCarroll
[5] doi:10.1523/jneurosci.2002-24.2026
Astrocyte TrkB.T1 Deficiency Disrupts Glutamatergic Synaptogenesis and Astrocyte-Synapse Interactions.
Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience
In common: mouse, cellular / molecular, 4 references
[6] doi:10.7554/elife.108071
The dual molecular identity of vestibular kinocilia bridges structural and functional traits of primary and motile cilia.
Journal: eLife
In common: mouse, cellular / molecular, 3 references
[7] doi:10.1038/s41593-026-02367-0 [code]
A reproducible three-dimensional model of human brain tissue to investigate physiological and disease-associated microglia phenotypes.
Journal: Nature neuroscience
In common: ggplot2, cellular / molecular, 3 references
[8] doi:10.1167/iovs.67.5.73 [code]
Identification of a Small-Molecule Modulator of Astrocyte Reactivity for Optic Nerve Protection.
Journal: Investigative ophthalmology & visual science
In common: ggplot2, mouse, cellular / molecular, 3 references
[9] doi:10.1038/s41467-026-71826-w
Signaling cascades shape functional subpopulations of cortical astrocytes in male wild-type mice and APP/PS1dE9 Alzheimer's disease model.
Journal: Nature communications
In common: mouse, cellular / molecular, 3 references
[10] doi:10.1016/j.bbi.2026.106824
Astrocyte reactivity by alcohol dependence in the central amygdala.
Journal: Brain, behavior, and immunity
In common: mouse, cellular / molecular, 3 references

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion, reproductions, activity

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.