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Record W4409317186 · doi:10.1073/pnas.2417400122

Astrocytic Ryk signaling coordinates scarring and wound healing after spinal cord injury

2025· article· en· W4409317186 on OpenAlexaff
Zhe Shen, Bo Feng, Wei Ling Lim, Timothy Woo, Yanlin Liu, Silvia Vicenzi, Jingyi Wang, Brian Kwon, Yimin Zou

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2025
Typearticle
Languageen
FieldMedicine
TopicSpinal Cord Injury Research
Canadian institutionsInternational Collaboration On Repair Discoveries
FundersNational Institute of Neurological Disorders and StrokeSchool of Medicine, University of California, San DiegoUniversity of California, San Diego
KeywordsAstrocyteSpinal cord injuryGlial scarWound healingCell biologyMicrogliaKnockout mouseSpinal cordConditional gene knockoutCell typeCell migrationCellNeuroscienceBiologyCentral nervous systemInflammationPhenotypeReceptorImmunologyBiochemistry

Abstract

fetched live from OpenAlex

Wound healing after spinal cord injury involves highly coordinated interactions among multiple cell types, which are poorly understood. Astrocytes play a central role in creating a border against the non-neural lesion core. To do so, astrocytes undergo dramatic morphological changes by first thickening and elongating their processes and then overlapping them to form a physical barrier. We show here that the expression of a cell-surface receptor, Ryk, is induced in astrocytes after injury in both rodent and human spinal cords. Astrocyte-specific knockout of Ryk dramatically elongated the reactive astrocytes, accelerated the formation of the border, and reduced the size of the scar. Astrocyte-specific knockout of Ryk also accelerated the injury responses of multiple cell types. Single-cell transcriptomics analyses revealed a broad range of changes in cell signaling among astrocytes, microglia, fibroblasts, and endothelial cells after astrocyte-specific Ryk knockout, suggesting that Ryk not only regulates injury responses of astrocytes but may also regulate signals emanating from astrocytes and coordinate the responses of these cell types. The elongation of astrocyte processes is mediated by NrCAM, a cell adhesion molecule induced by astrocyte-specific conditional knockout of Ryk after spinal cord injury. Our findings suggest that Ryk is a promising therapeutic target to accelerate wound healing, promote neuronal survival, and enhance functional recovery.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.002

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.059
GPT teacher head0.403
Teacher spread0.345 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations2
Published2025
Admission routes1
Has abstractyes

Explore more

Same venueProceedings of the National Academy of Sciences→Same topicSpinal Cord Injury Research→French-language works237,207→