Glial biology has evolved from viewing glia as passive support cells to understanding them as essential regulators of brain development, homeostasis, and disease. Microglia, astrocytes, oligodendrocytes, and their progenitors orchestrate synaptic pruning, circuit refinement, and myelination while coordinating immune and metabolic balance and maintaining neurovascular integrity. When these processes are perturbed, glial dysfunction contributes to a cascade of changes underlying developmental, neurodegenerative, and neuropsychiatric disorders. Despite major progress, central questions persist about how glial diversity adapts during development, ageing, and disease, and to what extent biological sex shapes these processes.
Recent advances in single-cell and spatial omics, live imaging, and human-relevant model systems now illuminate glial heterogeneity across regions, stages, and physiological states with unprecedented resolution. These tools reveal that glial states are dynamically remodelled by developmental cues, injury, experience, and sex-specific biological factors. Accumulating evidence points to distinct male and female trajectories in microglial maturation, astrocyte signalling, and oligodendrocyte differentiation that influence brain connectivity, vulnerability to inflammation, and therapeutic responsiveness. However, the molecular and cellular pathways underpinning these sex-dependent glial functions remain poorly understood, and their integration into broader frameworks of circuit and vascular development is just beginning to emerge.
This Research Topic aims to integrate developmental, cellular, and translational perspectives to define how glial heterogeneity evolves across the lifespan and contributes to neurological and psychiatric outcomes. The goal is to provide a comprehensive understanding of how region-specific, temporally dynamic, and sex-influenced glial states sustain neural and vascular homeostasis—or drive its breakdown—in disease. By highlighting multi-omic and human model approaches alongside developmental and regenerative neuroscience, this collection will connect glial mechanisms to neurocircuit and tissue-level function, promoting cross-disciplinary dialogue and therapeutic innovation.
To gather further insights into glial diversity across development and ageing, we welcome articles addressing, but not limited to, the following themes:
o Sex differences in glial development, function, and disease susceptibility, and their molecular or developmental drivers
o Glial heterogeneity across brain regions, developmental stages, and disease, resolved by single-cell, spatial, and multi-omic methods
o Microglial regulation of synaptic pruning, myelination, and circuit plasticity across the lifespan
o Astrocyte roles in neurotransmission, metabolic coupling, and homeostatic control in health and pathology
o Oligodendrocyte and OPC functions in myelination, remyelination, and circuit maturation
o Glial regulation of the blood–brain barrier, neurovascular unit, and vascular–immune interactions during development and degeneration
o Glial responses to injury, inflammation, and ageing within regenerative and neurodegenerative contexts
o Human cellular and organoid models that recapitulate glial diversity and sex-dependent mechanisms
o Therapeutic strategies targeting glial heterogeneity, neuroinflammatory pathways, or neurovascular dysfunction
Article types and fees
This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:
Brief Research Report
Case Report
Clinical Trial
Community Case Study
Data Report
Editorial
FAIR² Data
FAIR² DATA Direct Submission
General Commentary
Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.
Article types
This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:
Brief Research Report
Case Report
Clinical Trial
Community Case Study
Data Report
Editorial
FAIR² Data
FAIR² DATA Direct Submission
General Commentary
Hypothesis and Theory
Methods
Mini Review
Opinion
Original Research
Perspective
Review
Systematic Review
Technology and Code
Keywords: glial cells, glia–neuron interactions, microglia, astrocytes, oligodendrocytes, neuroinflammation, synaptic pruning, glial heterogeneity, neurovascular unit, blood-brain barrier, single-cell omics, spatial transcriptomics, sex differences in glia
Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
