Epigenetic and Gene-Regulatory Control of Glial Cells in Neurodevelopment and Neurodegeneration

Glial cells, including astrocytes, microglia, and oligodendrocytes, were long thought to play primarily supportive roles in the brain; however, they are increasingly recognized as active regulators of brain development, homeostasis, and responses to injury and disease. Aberrant glial activity can disrupt neuronal circuits and contribute to pathological outcomes, including neurodevelopmental disorders such as autism spectrum disorder and intellectual disability, as well as neurodegenerative diseases including Alzheimer’s, Parkinson’s, and ALS. Glial cells regulate synaptic connectivity, modulate immune responses, maintain metabolic and ionic balance, and shape plasticity throughout life. Despite growing interest, much research remains neuron-centric, potentially overlooking the full scope of glial contributions to brain disorders.Emerging evidence indicates that epigenetic and gene-regulatory mechanisms, including DNA methylation, histone modifications, chromatin accessibility, three-dimensional genome organization, and non-coding RNAs, are central to glial maturation and cell-state transitions. Dysregulation of these programs can drive maladaptive states, such as excessive neuroinflammation or impaired myelination, which in turn contribute to circuit dysfunction and disease progression. While many insights come from rodent models, human-specific glial epigenetic programs remain poorly understood.Recent technological advances, including single-cell and spatial transcriptomics, multi-omics approaches, and integrative computational analyses, now enable detailed characterization of glial states across development, degeneration, and injury. These tools allow researchers to address key questions: how do epigenetic programs control glial maturation and plasticity? How do injury, inflammation, or chronic stress reshape these programs? Which changes are reversible and represent potential therapeutic targets?Answering these questions will deepen our understanding of glial contributions to brain health and disease, and may reveal novel biomarkers and strategies to modulate glial states therapeutically.Goals:This Research Topic aims to advance our understanding of how epigenetic and gene-regulatory mechanisms shape glial function in neurodevelopmental disorders, neurodegenerative diseases, and related injury contexts. By bringing together studies using single-cell, spatial, and multi-omics approaches, as well as mechanistic and computational analyses, this collection seeks to identify key regulatory programs, uncover functional consequences for neurons and circuits, and inform therapeutic interventions.Scope and Information for Authors:- Epigenetic and gene-regulatory mechanisms controlling glial cell maturation, reactivity, and plasticity.- DNA methylation, histone modifications, chromatin accessibility, 3D genome organization, and non-coding RNAs in glial cell-state transitions.- Single-cell, spatial, and multi-omics approaches in human, organoid, or ex vivo models.- Functional outcomes of glial regulation, including synaptic and circuit activity, neuroinflammation, myelination, and neuronal survival.- Translational implications: biomarkers and strategies to reprogram harmful glial states.- This cross-disciplinary collection invites contributions from neuro-epigeneticists, glia biologists, systems neuroscientists, and computational biologists to advance our understanding of glial roles across brain disorders. Topic editors: Itzy E. Morales Pantoja, Yun Qian, Marissa Lisa Dubbelaar Source: https://www.frontiersin.org/research-topics/73581/epigenetic-and-gene-regulatory-control-of-glial-cells-in-neurodevelopment-and-neurodegeneration