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Editorial: 15 years of Frontiers in Cellular Neuroscience: exploring astrocyte heterogeneity: regional functions and impacts on diseases
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DOI：10.3389/fncel.2026.1951315.png)
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Abstract
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Two contributions focus on the diversity of astrocyte morphology and its relationship to function in the healthy brain. In their review; Ciani and Falcone (2024) examine interlaminar and varicose projection astrocytes; two morphotypes found predominantly in primates and humans. Unlike classical protoplasmic astrocytes; these cells display long; highly organized processes; suggesting that the evolution of astrocyte morphology may have contributed to the emergence of more complex brain functions. Moving beyond morphological description; Freund et al. (2024) classified 741 mouse hippocampal CA1 astrocytes into six distinct morphological groups and used detailed multi-compartment biophysical models to investigate their functional properties. They showed that astrocyte morphology strongly influences intracellular calcium responses to glutamate; affecting the amplitude and kinetics of calcium signals; whereas sodium and potassium dynamics were largely preserved across morphotypes. Together; these findings provide a direct mechanistic link between astrocyte structural heterogeneity and functional diversity. Two additional studies highlight how astrocyte heterogeneity emerges in disease. Using a mouse model of Huntington's disease; Brown et al. (2023) showed that GFAP⁺ and S100B⁺ astrocytes represent largely distinct populations that respond differently to pathology. In particular; GFAP⁺ astrocytes selectively accumulated in the dorsomedial striatum; where they clustered around white matter fascicles and were enriched in regions with a relatively low burden of mutant huntingtin aggregates. These findings emphasize the importance of considering both astrocyte subtype and anatomical location when studying reactive astrogliosis. Focusing on ischemic brain injury; Riew et al. (2023) demonstrated that reactive astrocytes; rather than microglia; are the main source of osteopontin in the hippocampus. Together with S100β; astrocyte-derived osteopontin promotes the formation of corpora amylacea-like structures from degenerating neuronal debris; supporting an active role for reactive astrocytes in tissue remodeling and debris clearance after injury.Finally; Pérez; Schummers and López-Hidalgo (2026) extend the concept of astrocyte heterogeneity to the subcellular level. Using graph-theoretical analysis of astrocytic calcium activity; they propose that individual astrocytic processes function as specialized input; output; and hub compartments; generating a hierarchical and directional flow of information. Their Perspective suggests that this functional organization is dynamically remodeled during development; aging; and disease; highlighting astrocytes as compartmentalized computational units rather than passive integrators. Together; these studies illustrate that astrocyte heterogeneity is a fundamental feature of brain organization; spanning multiple biological scales; from differences between species; brain regions; and molecular subtypes to functional specialization within individual cells. They also demonstrate how advances in imaging; molecular profiling; morphological reconstruction; and computational modeling are providing new opportunities to investigate astrocyte diversity and function. Understanding how astrocyte heterogeneity is established; maintained; and altered during disease will be essential for defining its biological significance and for identifying new therapeutic opportunities for neurological disorders. More broadly; these contributions reinforce the view that astrocyte heterogeneity is not merely a descriptive feature; but a fundamental principle of astrocyte biology that shapes brain function in both health and disease. We sincerely thank all the authors; reviewers; and readers who contributed to this Research Topic.
Keywords:
disease
glia
heterogeneity
astrocyte
physiology
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