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Record W4414477418 · doi:10.1038/s41590-025-02267-8

A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues

2025· article· en· W4414477418 on OpenAlexaff
Lloyd Steele, Bayanne Olabi, Kenny Roberts, Pavel Mazin, Simon Koplev, Catherine Tudor, Benjamin Rumney, Chloe Admane, Treasa Jiang, Donovan Correa‐Gallegos, Keerthi Priya Chakala, Aljes Binkevich, Nusayhah Hudaa Gopee, Alexander V. Predeus, Martin Prete, Elena Winheim, Karl Annusver, Agnes Forsthuber, Luc Francis, Sophie Frech, Clarisse Gânier, T. B. Layton, Yingzi Liu, Hao Yuan, Jóhann E. Guðjónsson, Beate M. Lichtenberger, Satveer K. Mahil, Jagdeep Nanchahal, Edel A. O’Toole, Maksim V. Plikus, Yuval Rinkevich, Emanuel Rognoni, Catherine Smith, Sarah A. Teichmann, Maria Kasper, April Foster, Mohammad Lotfollahi, Muzlifah Haniffa

Bibliographic record

VenueNature Immunology · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicSingle-cell and spatial transcriptomics
Canadian institutionsCanadian Institute for Advanced Research
FundersNational Institute of Arthritis and Musculoskeletal and Skin DiseasesWellcome TrustWellcome
KeywordsFibroblastHuman skinMyofibroblastReticular connective tissueDermal fibroblastImmune systemDermisGenomics

Abstract

fetched live from OpenAlex

Abstract Fibroblasts sculpt the architecture and cellular microenvironments of various tissues. Here we constructed a spatially resolved atlas of human skin fibroblasts from healthy skin and 23 skin diseases, with comparison to 14 cross-tissue diseases. We define six major skin fibroblast subtypes in health and three that are disease-specific. We characterize two fibroblast subtypes further as they are conserved across tissues and are immune-related. The first, F3: fibroblastic reticular cell-like fibroblast ( CCL19 + CD74 + HLA-DRA + ), is a fibroblastic reticular cell-like subtype that is predicted to maintain the superficial perivascular immune niche. The second, F6: inflammatory myofibroblasts ( IL11 + MMP1 + CXCL8 + IL7R + ), characterizes early human skin wounds, inflammatory diseases with scarring risk and cancer. F6: inflammatory myofibroblasts were predicted to recruit neutrophils, monocytes and B cells across multiple human tissues. Our study provides a harmonized nomenclature for skin fibroblasts in health and disease, contextualized with cross-tissue findings and clinical skin disease profiles.

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: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.005
GPT teacher head0.241
Teacher spread0.236 · 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 designObservational
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

Citations41
Published2025
Admission routes1
Has abstractyes

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