A human corticospinal organoid-slice connectoid model informs enhancer strategies for post-injury axon regrowth.
Overview
- John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
- Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
- MRC Laboratory of Molecular Biology, Cambridge, UK
- Division of Cognitive and Behavioral Neurology, Brigham & Women’s Hospital, Boston, MA, USA
- MRC-WT Cambridge Stem Cell Institute, Cambridge Biomedical Campus, Cambridge, UK
Abstract
Axon elongation in the mammalian central nervous system (CNS) declines during development, limiting regenerative capacity after birth. Intrinsic regulators of this process are promising repair targets, as immature axons can regrow in tissues otherwise not conducive to regeneration. Yet the precise timing and mechanisms underlying the cessation of axon growth in the human CNS remain unresolved. Here, we developed a three-dimensional human corticospinal motor organoid-slice connectoid platform mimicking the developmental axon elongation program and its subsequent restriction through maturation. Cortical and spinal slices establish functional connections while remaining spatially segregated, enabling cortical cell-type-specific observations without direct confounding effects by spinal cells. Using single-cell transcriptomics, computational analyses, axon regrowth assays, and live imaging, we identified transcriptional alterations contributing to decreased axon growth in maturing human cortical projection neurons. We further demonstrate that this decline can be reversed using compounds and repurposable drugs targeting a maturation-associated transcriptional shift, promoting post-injury axon repair.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.
The paper's code and data availability statement is in the Data section.
Tracing map
A tracing map links a paper to the code its authors published: this paper has none (its code is available on request), so it has no map.
Data
Datasets cited
- doi:10.17632/
zcvnhkjty3.1 — at the source; found in “Data and code availability”
Data and code availability
The SPORG scRNA-seq data generated in this work were deposited under accession number Gene Expression Omnibus (GEO): GSE285558 and are publicly available. Original western blot images have been deposited at Mendeley Data: https://
This paper does not report original code. Software availability is indicated in the text and in the key resources table.
This paper also analyzes existing, publicly available single-nucleus RNA-seq data derived from human fetal spinal cords, which is accessible under accession number GEO: GSE188516. In addition, the cortical organoid time point-related differential gene expression data used for meta-analysis in this work, a non-used subset of our previously collected dataset, are available in Data S2. For drug action predictions, the LINCS, DSigDB, and Proteomics databases were used through the Enrichr platform, which is freely accessible at https://
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 2, 28 September 2026
- Publisher: — → Cell Press
Version 1, 28 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 17 authors, 12 keywords, 5 MeSH terms, 4 funders, 60 references, 53 RRIDs.
Cite
This paper
Gibbons, G. M., Fuchsberger, T., Abdelgawad, M., Giandomenico, S. L., Szebényi, K., Petrova, V., Wenger, L. M., Olschewski, D. N., Chabros, J., Muresan, L., Feord, R. C., Asif, M., Fawcett, J. W., Mierau, S. B., Paulsen, O., Lancaster, M. A., & Lakatos, A. (2026). A human corticospinal organoid-slice connectoid model informs enhancer strategies for post-injury axon regrowth. Cell reports, 45(6), 117399. https://
BibTeX
@article{gibbons2026huma
author = {Gibbons, George M. and Fuchsberger, Tanja and Abdelgawad, Mai and Giandomenico, Stefano L. and Szebényi, Kornélia and Petrova, Veselina and Wenger, Lea M.D. and Olschewski, Daniel N. and Chabros, Jeremi and Muresan, Leila and Feord, Rachael C. and Asif, Muhammad and Fawcett, James W. and Mierau, Susanna B. and Paulsen, Ole and Lancaster, Madeline A. and Lakatos, András},
title = {{A human corticospinal organoid-slice connectoid model informs enhancer strategies for post-injury axon regrowth}},
journal = {Cell reports},
year = {2026},
month = may,
volume = {45},
number = {6},
pages = {117399},
publisher = {Cell Press},
issn = {2211-1247},
doi = {10.1016/
url = {https://
pmid = {42201810},
pmcid = {PMC7619264}
}
RIS
TY - JOUR
AU - Gibbons, George M.
AU - Fuchsberger, Tanja
AU - Abdelgawad, Mai
AU - Giandomenico, Stefano L.
AU - Szebényi, Kornélia
AU - Petrova, Veselina
AU - Wenger, Lea M.D.
AU - Olschewski, Daniel N.
AU - Chabros, Jeremi
AU - Muresan, Leila
AU - Feord, Rachael C.
AU - Asif, Muhammad
AU - Fawcett, James W.
AU - Mierau, Susanna B.
AU - Paulsen, Ole
AU - Lancaster, Madeline A.
AU - Lakatos, András
TI - A human corticospinal organoid-slice connectoid model informs enhancer strategies for post-injury axon regrowth
T2 - Cell reports
J2 - Cell Rep
PY - 2026
DA - 2026/
VL - 45
IS - 6
SP - 117399
SN - 2211-1247
PB - Cell Press
DO - 10.1016/
UR - https://
LA - en
ER -
CSL-JSON
{
"id": "10.1016/
"type": "article-journal",
"title": "A human corticospinal organoid-slice connectoid model informs enhancer strategies for post-injury axon regrowth",
"container-title": "Cell reports",
"author": [
{
"family": "Gibbons",
"given": "George M."
},
{
"family": "Fuchsberger",
"given": "Tanja"
},
{
"family": "Abdelgawad",
"given": "Mai"
},
{
"family": "Giandomenico",
"given": "Stefano L."
},
{
"family": "Szebényi",
"given": "Kornélia"
},
{
"family": "Petrova",
"given": "Veselina"
},
{
"family": "Wenger",
"given": "Lea M.D."
},
{
"family": "Olschewski",
"given": "Daniel N."
},
{
"family": "Chabros",
"given": "Jeremi"
},
{
"family": "Muresan",
"given": "Leila"
},
{
"family": "Feord",
"given": "Rachael C."
},
{
"family": "Asif",
"given": "Muhammad"
},
{
"family": "Fawcett",
"given": "James W."
},
{
"family": "Mierau",
"given": "Susanna B."
},
{
"family": "Paulsen",
"given": "Ole"
},
{
"family": "Lancaster",
"given": "Madeline A."
},
{
"family": "Lakatos",
"given": "András"
}
],
"container-title-short":
"volume": "45",
"issue": "6",
"page": "117399",
"DOI": "10.1016/
"PMID": "42201810",
"PMCID": "PMC7619264",
"ISSN": "2211-1247",
"publisher": "Cell Press",
"URL": "https://
"language": "en",
"issued": {
"date-parts": [
[
2026,
5,
26
]
]
}
}
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:10.7554/elife.98340 [code]
- Human adherent cortical organoids in a multi-well format.Journal: eLifeIn common: 4 references
- [2] doi:10.1126/sciadv.aec5080 [code]
- Label-free biochemical imaging and time point analysis of neural organoids via deep learning-enhanced Raman microspectroscopy.Journal: Science advancesIn common: developmental, 3 references
- [3] doi:10.1038/s41467-026-76569-2 [code]
- Self-organization of vascularized muscle from bovine embryonic stem cells.Journal: Nature communicationsIn common: 3 references
- [4] doi:10.1002/advs.202519893 [code]
- NeuroSuite for Long-Term Functional and Structural Studies of Air-Liquid Interface Cerebral Organoids.Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany)In common: developmental, 3 references
- [5] doi:10.1038/s41593-026-02316-x [code]
- Single-cell multi-omic atlas and morphogen screening informs midbrain and hindbrain organoid engineering.Journal: Nature neuroscienceIn common: 3 references
- [6] 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 neuroscienceIn common: 3 references
- [7] doi:10.1038/s41467-026-75273-5 [code]
- Spinal cord regeneration deploys cell-type specific developmental and non-developmental strategies to restore neuron diversity.Journal: Nature communicationsIn common: developmental, other condition, 2 references
- [8] doi:10.1002/advs.202522762 [code]
- Enhancing Maturation of Human Neuromuscular Organoids via Electrical Stimulation.Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany)In common: developmental, 2 references
- [9] doi:10.1038/s41586-026-10877-x [code]
- Human brain organoids record the passage of time over multiple years.Journal: NatureIn common: developmental, 2 references
- [10] doi:10.1039/d6tb01306f
- Hyaluronic acid-alginate hydrazone crosslinked hydrogels support the generation and maturation of V2a interneurons.Journal: Journal of materials chemistry. BIn common: developmental, 2 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.
Claim this paper
Correct its record
Say what each link of this record is, remove the ones that are not the paper's, add the ones that are missing. The correction becomes a new version of the record, in its Versions section.
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.