Evidence map›Paper›PMID 41864207›Full record

ArticleCell2026

Hyperinnervation inhibits organ-level regeneration in mammalian skin.

Hannah T Tam, Jingyu Peng, Rebecca Freeman, Yulia Shwartz, Shlomi Brielle, Sakshi Garg, Siti Rahmayanti, Stephen J Crocker, Devin Coon, Ya-Chieh Hsu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. The Role of the Nervous System in Lung Disease.Current neurology and neuroscience reports · 2026
    Review
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

10 authors.

Hannah T TamDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Jingyu PengDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Rebecca FreemanDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Yulia ShwartzDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Shlomi BrielleDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Sakshi GargDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Siti RahmayantiDivision of Plastic Surgery, Mass General Brigham and Harvard Medical School, Boston, MA 02115, USA.
Stephen J CrockerDepartment of Neuroscience, University of Connecticut School of Medicine, Farmington, CT 06030, USA.
Devin CoonDivision of Plastic Surgery, Mass General Brigham and Harvard Medical School, Boston, MA 02115, USA.
Ya-Chieh HsuDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Biology of Adversity Project, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: yachieh_hsu@harvard.edu.

Funding

Viral ModuleP30EY012196 · NEI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI ZHIGANG HE · 1998 to 2026
$21.3M
Rapid functional genetics to study stem cell-niche interactions in the skinR01AR080110 · NIAMS · HARVARD UNIVERSITY · PI Ya-Chieh Hsu · 2022 to 2026
$2.5M
Mechanisms of Fetal Skin RegenerationR01AR084566 · NIAMS · HARVARD UNIVERSITY · PI Ya-Chieh Hsu · 2024 to 2026
$1.4M
Molecular Mechanisms of Hormone-Mediated Sex Differences in Wound HealingR35GM157032 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Devin O'Brien-Coon · 2024 to 2026
$1.3M
Defining Sexual Dimorphism in the SkinF31AR083715 · NIAMS · HARVARD MEDICAL SCHOOL · PI FREEMAN, REBECCA JANE · 2024 to 2025
$80k
NEI NIH HHS P30 EY012196NIAMS NIH HHS F31 AR083715NIAMS NIH HHS R01 AR080110NIAMS NIH HHS R01 AR084566NIGMS NIH HHS R35 GM157032
6 · The paper itself

Abstract

Some mammalian tissues can replace lost cells within one lineage, but organ-level regeneration-restoring diverse cell types across lineages-remains rare. Here, we show that late embryonic full-thickness skin injuries heal by regenerating epithelial, mesenchymal, neuronal, and vascular tissues with proper connectivity. However, this ability is lost soon after birth, resulting in failure to restore most cell types and hyperinnervation within the wound bed. Single-cell sequencing identified a postnatal wound-specific fibroblast (PWF) population absent after embryonic wounding. Through an in vivo screen, we discovered that three PWF-enriched genes-Timp1, Cxcl12, and Ccl7-inhibit organ-level regeneration and cause hyperinnervation when overexpressed in embryonic wounds. Reducing hyperinnervation in postnatal wounds through the depletion of Cxcl12 in fibroblasts or nerve ablation enables regeneration of diverse lineages after injury. Our study identifies mechanisms that transition an organ from regenerative to non-regenerative, discovers fibroblast-driven hyperinnervation as a key barrier, and demonstrates that removing this barrier unlocks organ-level regeneration.

Indexed as

RegenerationSkinWound HealingAnimalsChemokine CXCL12FemaleFibroblastsMiceMice, Inbred C57BLTissue Inhibitor of Metalloproteinase-1Chemokine CXCL12Cxcl12 protein, mouseTissue Inhibitor of Metalloproteinase-1Cxcl12hyperinnervationinjury repairnerve-tissue interactionsorgan-level regenerationregenerationwound healing

Identifiers

PMID41864207
PMCPMC13082877

What OpenQuestion holds

Textmetadata
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Read underepoch 390

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.