Astrocytes were thought to serve only supportive functions; however, they are increasingly recognized as key participants in shaping brain development and modulating plasticity through creating and removing synaptic connections. Aberrant astrocyte activity can disrupt the brain circuitry, potentially contributing to neurodevelopmental disorders such as autism and schizophrenia 1–3. These glial cells maintain metabolic and ionic balance and modulate immune responses throughout life. Yet, despite growing interest in astrocytes, a neuron-centric focus still predominates, potentially obscuring the depth of astrocytic contributions to brain disorders. In both neurodevelopmental disorders such as autism spectrum disorders (ASD) and schizophrenia, and in neurodegenerative diseases like Alzheimer’s, Parkinson’s, and ALS, astrocytes adopt reactive states that profoundly influence neuronal survival and circuit function 4,5. Thus, understanding how neurons and astrocytes interact across health and disease remains essential for developing comprehensive therapeutic strategies.

Over the past decade, studies have revealed that astrocyte dysfunction is not merely reactive but may also contribute directly to disease onset and progression. Studies have shown that astrocytic dysfunction contributes to circuit disruption, altered synaptic pruning, and sustained neuroinflammation 6,7. Epigenetic mechanisms, including chromatin remodeling, DNA methylation, histone modification, and regulation by non-coding RNAs, are emerging as key drivers 8–11. However, most of this work is based on rodent models, limiting our understanding of human-specific epigenetic programs.

Recent advances in single-cell multi-omics, spatial transcriptomics, and human-derived brain organoids now provide the tools to dissect astrocyte states across developmental and degenerative contexts 9,11 . These technologies open the door to address major questions: (1) How do epigenetic programs guide astrocyte maturation and plasticity during critical periods of development? (2) How do chronic stressors, such as inflammation or aging, reshape these programs to drive disease? (3) Which changes are reversible and represent therapeutic targets?

Answering these questions will deepen our understanding of brain health across the lifespan and may reveal new biomarkers and intervention strategies for conditions ranging from ASD to Alzheimer’s.

Goals

This Research Topic aims to advance our understanding of how epigenetic regulation shapes astrocyte function in neurodevelopmental and neurodegenerative disorders. By bringing together studies using human-derived models, single-cell and spatial omics, and mechanistic approaches, this collection seeks to identify key molecular programs, uncover therapeutic targets, and bridge the gap between developmental and degenerative neuropathology.

Scope and Information for Authors

- Epigenetic regulation of astrocyte development, maturation, and plasticity.

- Chromatin accessibility, DNA methylation, histone modification, and non-coding RNA in astrocyte state transitions.

- Single-cell and spatial multi-omics approaches in human brain organoids or ex vivo models.

- Astrocyte-driven circuit dysfunction in neurodevelopmental (ASD, schizophrenia) and neurodegenerative (MS, Alzheimer’s, Parkinson’s, ALS) disorders.

- Translational implications: biomarkers and strategies to reverse maladaptive astrocyte states.

This cross-disciplinary collection invites contributions from neuro-epigeneticists, glia biologists, systems neuroscientists, and bioengineers to help advance our understanding of the astrocyte roles across brain disorders.

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Epigenetic Regulation of Astrocytes in Neurodevelopmental and Neurodegenerative Disorders