Epigenetic Regulation of Cell Differentiation During Development and Disease: From Vascular Plasticity to Immune Signaling

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 31 December 2026 | Viewed by 3533

Special Issue Editors


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Guest Editor
Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET, Universidad Nacional de Córdoba, Córdoba, Argentina
Interests: epigenetics; cardiovascular research; smooth muscle cells

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Guest Editor
1. Department of Experimental Pathology, Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas, Institut d'Investigacions Biomédiques August Pi i Sunyer, Barcelona, Spain
2. Biomedical Research Networking Center in Respiratory Diseases (CIBERES), Madrid, Spain
Interests: COPD; pulmonary hypertension; pulmonary fibrosis; ARDS; ALI; OSAS
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Special Issue Information

Dear Colleagues,

Introduction and Scope

The traditional view of cellular identity as a static state has been revolutionized by our understanding of phenotypic plasticity. In the cardiovascular and immune systems, the ability of a cell to remodel its identity is a double-edged sword; it is essential for embryonic morphogenesis and wound healing, yet it serves as a primary driver of pathologies such as atherosclerosis, hypertension, and fibrosis.

Central to this flexibility is epigenetic regulation. Modifications to the chromatin landscape, including DNA methylation, histone tail modifications, non-coding RNA interactions, and epitranscriptomics, play a key role orchestrating gene expression program without altering the underlying genetic code.

Focus Areas

This Special Issue aims to move beyond isolated cell models to explore the complex epigenetic networks governing:

  • Vascular Smooth Muscle Cells (vSMCs): While vSMCs are critical for maintaining vascular tone and stability, they exhibit extreme plasticity. Beyond the classical "contractile-to-synthetic" switch, recent lineage tracing and scRNA-seq data have shown vSMCs can transition into osteoblast-like, macrophage-like, or mesenchymal-like states.
  • Endothelial-to-Mesenchymal Transition (EndoMT): We seek to explore the epigenetic triggers that cause endothelial cells to lose their polar identity and acquire a myofibroblastic phenotype, a process central to tissue fibrosis and vascular remodeling.
  • Immune Cell Differentiation: We welcome studies on the role of "epigenetic memory" in immune cells as they differentiate and infiltrate diseased vascular tissues, contributing to chronic inflammation.
  • Development vs. Disease: Comparative studies on how epigenetic mechanisms used during embryonic development are "reawakened" or dysregulated in adult pathological states.

Dr. Melina M. Musri
Dr. Victor I. Peinado
Guest Editors

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Keywords

  • vascular smooth muscle cells
  • cell phenotypic change
  • epigenetics
  • gene expression regulation
  • cell differentiation

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Published Papers (2 papers)

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Review

33 pages, 2103 KB  
Review
Chromatin Remodeling in VSMC Phenotype Switching During Vascular Remodeling: From Mechanism to Therapeutic Potential
by Xiaozhu Ma, Shuai Mei, Qidamugai Wuyun, Li Zhou, Hu Ding and Jiangtao Yan
Biomolecules 2026, 16(2), 265; https://doi.org/10.3390/biom16020265 - 7 Feb 2026
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Abstract
Vascular remodeling is a characteristic pathological feature of various vascular diseases, including atherosclerosis, restenosis following vascular injury, hypertension, and aneurysms. The phenotypic switching of vascular smooth muscle cells (VSMCs) acts as a key driver of vascular remodeling. Under specific pathological stimuli, VSMCs rapidly [...] Read more.
Vascular remodeling is a characteristic pathological feature of various vascular diseases, including atherosclerosis, restenosis following vascular injury, hypertension, and aneurysms. The phenotypic switching of vascular smooth muscle cells (VSMCs) acts as a key driver of vascular remodeling. Under specific pathological stimuli, VSMCs rapidly transition from a contractile to a dedifferentiated phenotype, characterized by enhanced proliferation, migration, and secretory activity. Chromatin remodeling, a core mechanism of epigenetic regulation, orchestrates dynamic changes in chromatin structure and function through ATP-dependent remodeling complexes, histone-modifying enzymes, and DNA methyltransferases. These components collectively translate mechanical stress, metabolic disturbances, and inflammatory signals into reversible epigenetic modifications, thereby precisely regulating VSMC phenotypic switching. As such, chromatin remodeling represents a critical node for therapeutic intervention in vascular remodeling-related diseases. In recent years, a growing body of research has focused on the role of chromatin remodelers in regulating VSMC phenotype. In this review, we focus on the roles of ATP-dependent chromatin-remodeling factors and chromatin-modifying enzymes in the control of gene expression of VSMC phenotype switching. Firstly, we summarize the latest insights into chromatin remodeling and VSMC phenotypic switching, and then discuss recent advances in the identification and functional characterization of chromatin remodeling molecules, emphasizing their implications for VSMC behavior. Finally, we highlight the translational potential of targeting chromatin remodelers in the development of clinical therapies for vascular remodeling diseases and outline future directions for research in this field. Full article
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45 pages, 4315 KB  
Review
A Comprehensive Review of Epigenetic Regulation of Vascular Smooth Muscle Cells During Development and Disease
by Lautaro Natali, Benjamín de la Cruz-Thea, Andrea Godino, Cecilia Conde, Victor I. Peinado and Melina M. Musri
Biomolecules 2026, 16(1), 173; https://doi.org/10.3390/biom16010173 - 21 Jan 2026
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Abstract
Vascular smooth muscle cells (VSMCs) in the tunica media are essential for maintaining the structure and function of the arterial wall. These cells regulate vascular tone and contribute to vasculogenesis and angiogenesis, particularly during development. Proper control of VSMC differentiation ensures the correct [...] Read more.
Vascular smooth muscle cells (VSMCs) in the tunica media are essential for maintaining the structure and function of the arterial wall. These cells regulate vascular tone and contribute to vasculogenesis and angiogenesis, particularly during development. Proper control of VSMC differentiation ensures the correct size and patterning of vessels. Dysregulation of VSMC behaviour in adulthood, however, is linked to serious cardiovascular diseases, including aortic aneurysm, coronary artery disease, atherosclerosis and pulmonary hypertension. VSMCs are characterised by their phenotypic plasticity, which is the capacity to transition from a contractile to a synthetic, dedifferentiated state in response to environmental cues. This phenotypic switch plays a central role in vascular remodelling, a process that drives the progression of many vascular pathologies. Epigenetic mechanisms, which are defined as heritable but reversible changes in gene expression that do not involve alterations to the DNA sequence, have emerged as key regulators of VSMC identity and behaviour. These mechanisms include DNA methylation, histone modifications, chromatin remodelling, non-coding RNA and RNA modifications. Understanding how these epigenetic processes influence VSMC plasticity is crucial to uncovering the molecular basis of vascular development and disease. This review explores the current understanding of VSMC biology, focusing on epigenetic regulation in health and pathology. Full article
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