Evidence map›Paper›PMID 40816279›Full record

ArticleCell stem cell2025

Multi-omic analysis reveals retinoic acid molecular drivers for dermal fibrosis and regenerative repair in the skin.

Michelle Griffin, Jason L Guo, Jennifer B L Parker, Maxwell Kuhnert, Dayan J Li, Caleb Valencia, Annah Morgan, Mauricio Downer, Asha C Cotterell, John M Lu and 6 more

Abstract read
In one paragraph

Article in Cell stem cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026
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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

16 authors.

Michelle GriffinDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Jason L GuoDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Jennifer B L ParkerDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Maxwell KuhnertDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Dayan J LiDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Caleb ValenciaDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Annah MorganDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Mauricio DownerDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Asha C CotterellDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
John M LuDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Sarah DilorioInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Khristian Eric Bauer-Rowe RamosInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Michael JanuszykDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Howard Y ChangDepartment of Dermatology and Genetics, Stanford University School of Medicine, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Derrick C WanDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: dwan@stanford.edu.
Michael T LongakerDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: longaker@stanford.edu.

Funding

Center for Dental, Oral, and Craniofacial Tissue and Organ Regeneration (C-DOCTOR)U24DE029463 · NIDCR · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHAI, YANG, LOTZ, JEFFREY C. · 2020 to 2024
$29.5M
Center for Personal Dynamic RegulomesRM1HG007735 · NHGRI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2019 to 2023
$13.8M
Reprogramming fibroblasts embryonic origins to overcome skin fibrosis and scarring.R01DE032677 · NIDCR · STANFORD UNIVERSITY · PI MICHAEL T LONGAKER, Derrick Wan · 2023 to 2026
$1.4M
Defining the role of mechanoresponsive adipocyte-to-fibroblast transition in wound fibrosis.R01AR081343 · NIAMS · STANFORD UNIVERSITY · PI MICHAEL T LONGAKER, Derrick Wan · 2023 to 2026
$1.3M
Mechanoresponsive Engrailed-1-negative fibroblasts activate Engrailed-1 to promote fibrosis in wound healingR01GM136659 · NIGMS · STANFORD UNIVERSITY · PI LONGAKER, MICHAEL T · 2020 to 2023
$1.3M
Spatiotemporal Atlas of Cellular Networks and Ultrastructural States Mediating the Progression and Resolution of Pulmonary FibrosisF32HL167318 · NHLBI · STANFORD UNIVERSITY · PI GUO, JASON LIWEI · 2023 to 2024
$146k
NHGRI NIH HHS RM1 HG007735NHLBI NIH HHS F32 HL167318NIAMS NIH HHS R01 AR081343NIDCR NIH HHS R01 DE032677NIDCR NIH HHS U24 DE029463NIGMS NIH HHS R01 GM136659
6 · The paper itself

Abstract

Skin fibrosis is driven by fibroblast activation and excessive extracellular matrix deposition. To ascertain the fibroblast subpopulation(s) responsible for instigating fibrosis, we employed an established murine bleomycin skin fibrosis model. We characterized both the fibrotic and remodeling phases of dermal fibrosis through a multi-omic approach. Using an unsupervised machine learning algorithm that quantifies 294 fiber features, we identified precise time points of fibrosis and regeneration. Single-cell transcriptomic and epigenomic sequencing then identified a Cyp26b1-expressing fibroblast subpopulation responsible for dermal fibrosis. The same fibroblast subtype was mapped to Visium spatial transcriptomic data. We further mapped the fibrotic subtypes to protein spatial data. To ascertain the functional impact of the fibroblast subpopulations, transplant delivery analysis showed their ability to drive skin fibrosis. Lastly, we identified a small molecular inhibitor of Cyp26b1 (talarozole) that prevents and rescues dermal fibrosis. Conclusively, we establish an atlas of the fibrotic and regenerative biological drivers of skin fibrosis.

Indexed as

RegenerationSkinTretinoinAnimalsBleomycinFibroblastsFibrosisMiceMice, Inbred C57BLMultiomicsRetinoic Acid 4-HydroxylaseBleomycinRetinoic Acid 4-HydroxylaseTretinoinCyp26b1fibroblastsmulti-omicretinoic acidsingle-cell sequencingskin fibrosisspatial transcriptomictranscriptomicsvitamin Awound healing

Identifiers

PMID40816279
PMCPMC12373384

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.