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A transcriptomic atlas of astrocyte heterogeneity across space and time in mouse and marmoset

ABSTRACT: 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.

ORGANISM(S): Mus musculus Callithrix jacchus

PROVIDER: GSE309702 | GEO | 2025/11/20

REPOSITORIES: GEO

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Project description:MartínJiménez2017 - Genome-scale reconstruction of the human astrocyte metabolic network This model is described in the article: Genome-Scale Reconstruction of the Human Astrocyte Metabolic Network. Martín-Jiménez CA, Salazar-Barreto D, Barreto GE, González J. Front Aging Neurosci 2017; 9: 23 Abstract: Astrocytes are the most abundant cells of the central nervous system; they have a predominant role in maintaining brain metabolism. In this sense, abnormal metabolic states have been found in different neuropathological diseases. Determination of metabolic states of astrocytes is difficult to model using current experimental approaches given the high number of reactions and metabolites present. Thus, genome-scale metabolic networks derived from transcriptomic data can be used as a framework to elucidate how astrocytes modulate human brain metabolic states during normal conditions and in neurodegenerative diseases. We performed a Genome-Scale Reconstruction of the Human Astrocyte Metabolic Network with the purpose of elucidating a significant portion of the metabolic map of the astrocyte. This is the first global high-quality, manually curated metabolic reconstruction network of a human astrocyte. It includes 5,007 metabolites and 5,659 reactions distributed among 8 cell compartments, (extracellular, cytoplasm, mitochondria, endoplasmic reticle, Golgi apparatus, lysosome, peroxisome and nucleus). Using the reconstructed network, the metabolic capabilities of human astrocytes were calculated and compared both in normal and ischemic conditions. We identified reactions activated in these two states, which can be useful for understanding the astrocytic pathways that are affected during brain disease. Additionally, we also showed that the obtained flux distributions in the model, are in accordance with literature-based findings. Up to date, this is the most complete representation of the human astrocyte in terms of inclusion of genes, proteins, reactions and metabolic pathways, being a useful guide for in-silico analysis of several metabolic behaviors of the astrocyte during normal and pathologic states. This model is hosted on BioModels Database and identified by: MODEL1608180000. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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A transcriptomic atlas of astrocyte heterogeneity across space and time in mouse and marmoset

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