Evidence map›Paper›PMID 40950147›Full record

ArticlebioRxiv : the preprint server for biology2025

Single-vessel transcriptome map pathological landscapes and reveal NR2F2-mediated smooth muscle cell phenotype acquisition in capillary malformations.

Vi Nguyen, Irving Mao, Siwuxie He, Isabella Castellanos, Mackenzie Azuero, Marcelo L Hochman, Yin Rong, Laena Pernomian, Elliott H Chen, Harold I Friedman and 9 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

19 authors.

Vi NguyenDepartment of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina 29209, USA.ORCID 0000-0002-0688-0286
Irving MaoDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
Siwuxie HeDepartment of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina 29209, USA.
Isabella CastellanosDepartment of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina 29209, USA.
Mackenzie AzueroDepartment of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina 29209, USA.
Marcelo L HochmanThe Facial Surgery Center and the Hemangioma & Malformation Treatment Center, Charleston, South Carolina 29425, USA.
Yin RongDepartment of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina 29209, USA.
Laena PernomianDepartment of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina 29209, USA.ORCID 0000-0003-3930-0919
Elliott H ChenDivision of Plastic Surgery, School of Medicine, University of South Carolina, Columbia, South Carolina 29203, USA.
Harold I FriedmanDivision of Plastic Surgery, School of Medicine, University of South Carolina, Columbia, South Carolina 29203, USA.
Yan-Hua ChenDepartment of Biochemistry, University of South Carolina, Columbia, South Carolina 29208, USA.
Qun LuDepartment of Biochemistry, University of South Carolina, Columbia, South Carolina 29208, USA.
Daping FanDepartment of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina 29209, USA.
Camilla F WenceslauDepartment of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina 29209, USA.ORCID 0000-0002-0815-3568
Dong-Bao ChenDepartment of Obstetrics and Gynecology, University of California, Irvine, Irvine, California 92617, USA.ORCID 0000-0002-1067-6018
J Stuart NelsonDepartments of Surgery and Biomedical Engineering, Beckman Laser Institute and Medical Clinic, University of California, Irvine, Irvine, California 92617, USA.
Anil G JeggaDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
Yunguan WangDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.ORCID 0000-0003-0767-6188
Wenbin TanDepartment of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina 29209, USA.ORCID 0000-0002-2334-8988

Funding

Formyl peptide receptor activation induces vascular plasticity and remodeling inhypertensionR01HL149762 · NHLBI · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI WENCESLAU, CAMILLA FERREIRA · 2021 to 2025
$1.9M
Vascular Pathogenesis of Port Wine StainR01AR073172 · NIAMS · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI TAN, WENBIN · 2018 to 2022
$1.5M
Intrarenal Arteries Sense N-formyl Peptides Leading to Vascular Injury in SepsisR00GM118885 · NIGMS · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI WENCESLAU, CAMILLA FERREIRA · 2019 to 2021
$746k
Generation and Validation of Disease Models for Port-Wine BirthmarksR21AR083066 · NIAMS · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI TAN, WENBIN · 2023 to 2024
$356k
NHLBI NIH HHS R01 HL149762NIAMS NIH HHS R01 AR073172NIAMS NIH HHS R21 AR083066NIGMS NIH HHS R00 GM118885
6 · The paper itself

Abstract

Background: Capillary malformation (CM) is a congenital vascular anomaly affecting the skin, mucosa, and brain, yet the understanding of its vascular pathogenesis remains limited. Methods: We applied spatial whole-transcriptome profiling (GeoMx) and gene set enrichment analysis within CM lesions at single vasculature level. Differentially expressed genes were validated by immunofluorescence staining. Phosphoproteomics was profiled to uncover lesion-wide phosphorylation sites on proteins. Single-cell RNA sequencing was performed on CM-derived induced pluripotent stem cells (iPSCs) to determine differentiation trajectories of lesional vascular lineages. In silico gene perturbation was used to predict candidate genes for modulating vascular pathological progression, followed by functional validation in CM iPSC-derived endothelial cells (ECs) using a Tet-on system. Results: A spatial transcriptomic atlas was constructed, and pathological landscape of individual CM vasculature was delineated. CM vessels exhibited hallmarks of endothelial-to-mesenchymal transition (EndMT), including disruption of adherens junctions (AJs), vascular identity transitions, and metabolic remodeling. Phosphoproteomics confirmed that differentially phosphorylated proteins were enriched in EndMT- and AJ-related pathways. Aberrant expression of venous transcriptional factor NR2F2 was observed in lesional ECs and correlated with progressive enlargement from capillaries to larger-caliber vessels containing multiple layers of smooth muscle cells (SMCs). In CM iPSCs, differentiation course yielded reduced ECs but increased SMCs. Conclusions: Single CM vasculature displays pathological hallmarks characterized by EndMT and AJ disruption, leading to progressive vascular remodeling. NR2F2 functions as a central regulatory factor orchestrating the acquisition of the SMC phenotype, thereby representing a potential therapeutic target in CM.

Indexed as

adherens junctionsCapillary malformationendothelial cellsendothelial-to-mesenchymal transitioninduced pluripotent stem cellsNR2F2whole transcriptome atlas

Identifiers

PMID40950147
PMCPMC12424823

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.