Evidence map›Paper›PMID 41167421›Full record

ArticleJournal of advanced research2026

Vinculin mediates a dynamic signal flow underlying cardiac outflow tract development as revealed by single-cell and spatial transcriptomic analysis.

Reeson Xu Wang, Mingxuan Liang, Xixin Wang, Yan Pan, Zhixin Li, Chi-Chung Hui, Kyoung-Han Kim, Asif Javed, Elly Sau-Wai Ngan

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Article in Journal of advanced research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Elucidating Gene Functions in Congenital Heart Disease.Current treatment options in cardiovascular medicine · 2026
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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Reeson Xu WangDepartment of Surgery, The University of Hong Kong, Pokfulam, Hong Kong.
Mingxuan LiangSchool of Biomedical Science, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
Xixin WangDepartment of Surgery, The University of Hong Kong, Pokfulam, Hong Kong.
Yan PanSchool of Biomedical Science, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
Zhixin LiDepartment of Surgery, The University of Hong Kong, Pokfulam, Hong Kong.
Chi-Chung HuiProgram in Developmental & Stem Cell Biology, The Hospital for Sick Children and Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 0A4, Canada.
Kyoung-Han KimUniversity of Ottawa Heart Institute and Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1Y 4W7, Canada.
Asif JavedSchool of Biomedical Science, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong. Electronic address: javed@hku.hk.
Elly Sau-Wai NganDepartment of Surgery, The University of Hong Kong, Pokfulam, Hong Kong. Electronic address: engan@hku.hk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionCardiac outflow tract (OFT) development relies on the interactions among cardiac neural crest cells (CNCC) and the second heart field (SHF) cells. However, the molecular signals underlying these interactions remain largely unclear.

objectivesVinculin (VCL) is an adaptor protein for focal adhesions, which integrates various external signals and mediates cell-cell communications, representing a potential hub gene directing the OFT development. Here, we aimed to build a holistic map of signal flows underlying CNCC-directed OFT development using neural crest-specific Vcl knockout mouse mutants (Vcl cKO).

methodsWe validated the OFT defects of Vcl cKO mutants by performing various immunohistochemistry analyses. Subsequent high-resolution transcriptomic analysis reconstructed the differentiation trajectory of CNCCs along the vascular smooth muscle (VSMC) lineage. The spatial RNA-seq further aligned the transcriptomes of OFT cells with their spatial patterns to explore the cell interaction dynamics among OFT cells. Exploiting human pluripotent stem cell (hPSC)-based in vitro differentiation assays, the signaling pathways underlying Vcl-mediated CNCC progression along the VSMC lineage were defined.

resultsVcl cKO exhibited malformation of pharyngeal arch arteries, OFT septation defects and hyperplastic semilunar valves, due to defects in migration and vascular smooth muscle (VSMC) lineage differentiation of CNCCs, which prohibited the subsequent myocardialization, perturbing the OFT and valve remodeling. High-resolution transcriptomic analysis revealed that CNCC-to-VSMC differentiation is orchestrated by Vcl-dependent p38 and Tgf-β signalings. Multimodal analysis integrating the single-cell and spatial transcriptomes of OFT cells further suggested a shift of signal flow among OFT cells and loss of cell-extracellular matrix interaction perturb OFT morphogenesis.

conclusionIn sum, dynamic signal flows among CNCC and SHF cells guide OFT remodeling, in which p38-Tgf-β signaling mediates the VSMC lineage differentiation of CNCCs, and timely regulates their interactions with SHF-derived cells through ECM.

Indexed as

HeartVinculinAnimalsCell DifferentiationHumansMiceMice, KnockoutMuscle, Smooth, VascularNeural CrestSignal TransductionSingle-Cell AnalysisSingle-Cell Gene Expression AnalysisSpatial TranscriptomicsTranscriptomeVcl protein, mouseVinculinCardiac neural crest cellOutflow tractSingle cell transcriptomicsSpatial transcriptomicsTransforming growth factor-beta, extracellular matrixVinculin

Identifiers

PMID41167421
PMCPMC13316539

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.