Wednesday, December 10, 2025

Astrocyte diversity across four brain regions and six brain development stages and two species, a new atlas

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"The most abundant of the brain’s non-neuronal cells are astrocytes, star-shaped cells with a lot of responsibilities. Astrocytes help shape neural circuits, participate in information processing, and provide nutrient and metabolic support to neurons. Individual cells can take on new roles throughout their lifetimes, and at any given time, the astrocytes in one part of the brain will look and behave differently than the astrocytes somewhere else. ...

collected brain cells from mice and marmosets at six stages of life, spanning embryonic development to old age. For each animal, they sampled cells from four different brain regions: the prefrontal cortex, the motor cortex, the striatum, and the thalamus. ...

After assessing the transcriptomes of about 1.4 million brain cells, the group focused in on the astrocytes, analyzing and comparing their patterns of gene expression. At every life stage, from before birth to old age, the team found regional specialization: astrocytes from different brain regions had similar patterns of gene expression, which were distinct from those of astrocytes in other brain regions.

This regional specialization was also apparent in the distinct shapes of astrocytes in different parts of the brain, which the team was able to see with expansion microscopy ...

Notably, the astrocytes in each region changed as animals matured. ...

The most dramatic changes the team detected occurred between birth and early adolescence, a period during which brains rapidly rewire as animals begin to interact with the world and learn from their experiences. ..."

From the highlights and abstract:
"Highlights
• A transcriptomic atlas across brain regions and development in mouse and marmoset
• Astrocyte regional heterogeneity evolves over postnatal development
• Astrocyte transcriptomes are broadly conserved across species with divergent signatures
• Expansion microscopy reveals regional distinctions in astrocyte morphology

Summary
How astrocyte regionalization unfolds over development is not fully understood. We used single-nucleus RNA sequencing to characterize the molecular diversity of brain cells across six developmental stages and four brain regions in the mouse and marmoset brain.
Our analysis revealed striking regional heterogeneity among astrocytes, particularly between telencephalic and diencephalic regions in both species. Most of the region patterning was private to astrocytes and not shared with neurons or other glial types.
Though astrocytes were already regionally patterned in late embryonic stages, this region-specific astrocyte gene expression signature changed significantly over postnatal development, and its composition suggests that regional astrocytes further specialize postnatally to support their local neuronal circuits.
Across mouse and marmoset, we found hundreds of species-differentially expressed genes and divergence in the expression of astrocytic region- and age-differentially expressed genes. Finally, we used expansion microscopy to show that astrocyte morphology is also regionally specialized."

Astrocyte diversity across space and time | MIT News | Massachusetts Institute of Technology



Graphical abstract


Figure 1 A multi-region transcriptomic atlas of brain cell diversity across postnatal development in marmoset and mouse


Figure 7 Expansion microscopy of virally labeled astrocytes in the mouse and marmoset brain


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