Evidence map›Paper›PMID 41331142›Full record

ArticleNature neuroscience2026

The regulatory code of injury-responsive enhancers enables precision cell-state targeting in the CNS.

Margherita Zamboni, Adrián Martínez-Martín, Gabriel Rydholm, Timm Häneke, Laura Pintado Almeida, Deniz Seçilmiş, Christoph Ziegenhain, Enric Llorens-Bobadilla

Abstract read
In one paragraph

Article in Nature neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Margherita ZamboniDepartment of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-0664-4707
Adrián Martínez-MartínDepartment of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.ORCID http://orcid.org/0009-0008-2335-6460
Gabriel RydholmDepartment of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.ORCID http://orcid.org/0009-0006-1667-1214
Timm HänekeDepartment of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-9734-8307
Laura Pintado AlmeidaDepartment of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.
Deniz SeçilmişDepartment of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.
Christoph ZiegenhainDepartment of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-2208-4877
Enric Llorens-BobadillaDepartment of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden. enric.llorens@ki.se.ORCID http://orcid.org/0000-0002-7891-1272

Funding

EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) EnhanceRegenKnut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation) WASP-DDLSStiftelsen för Strategisk Forskning (Swedish Foundation for Strategic Research) FFL21-0278Svenska Sällskapet för Medicinsk Forskning (Swedish Society for Medical Research) Postdoctoral fellowshipVetenskapsrådet (Swedish Research Council) Starting GrantWings for Life (Wings for Life Research Foundation)
6 · The paper itself

Abstract

Enhancer elements direct cell-type-specific gene expression programs. After injury, cells change their transcriptional state to adapt to stress and initiate repair. Here we investigate how injury-induced transcriptional programs are encoded within enhancers in the mammalian CNS. Leveraging single-nucleus transcriptomics and chromatin accessibility profiling, we identify thousands of injury-induced, cell-type-specific enhancers in the mouse spinal cord after a contusion injury. These are abundant in glial cells and retain cell-type specificity, even when regulating shared wound response genes. By modeling glial injury-responsive enhancers using deep learning, we reveal that their architecture encodes cell-type specificity by integrating generic stimulus response elements with cell identity programs. Finally, through in vivo enhancer screening, we demonstrate that injury-responsive enhancers can selectively target reactive astrocytes across the CNS using therapeutically relevant gene delivery vectors. Our decoding of the principles of injury-responsive enhancers enables the design of sequences that can be programmed to target disease-associated cell states.

Indexed as

Central Nervous SystemEnhancer Elements, GeneticSpinal Cord InjuriesAnimalsAstrocytesMiceMice, Inbred C57BLNeuroglia

Identifiers

PMID41331142
PMCPMC12880913

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.