The Role of Astrocyte-Neuron Interactions in Shaping Neuronal Maturation during Human Brain Development.

Overview

1. State Key Laboratory of Brain Function and Disorders, MOE Frontiers Center for Brain Science, Institutes of Brain Science and Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200032, China
2. Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China

Abstract

The human brain undergoes extensive transcriptomic remodeling during the perinatal period and early postnatal development, yet the cellular basis and regulatory logic underlying these changes remain unclear. By integrating single-cell and bulk RNA sequencing data across 9 developmental stages of the human cerebral cortex, we systematically characterized the temporal dynamics of gene expression across major cell types. From late fetal stages to infancy, pronounced transcriptomic changes occur, accompanied by shifts in cellular composition and gene expression programs. During this period, glial cells exhibit gene expression patterns and computationally inferred signaling features consistent with ongoing neuronal maturation. Cell–cell communication analysis further suggests that astrocyte subtypes exhibit distinct interaction patterns with neurons, characterized by subtype-specific temporal dynamics and lineage-associated features. Comparative analyses with mouse brains reveal human-specific features in synaptogenesis and axonogenesis that coincide with the evolutionary divergence of astrocyte subtypes. In addition, immature and mature astrocyte subtypes show distinct associations with neuronal maturation, and their developmental transitions align with stages of increased transcriptomic divergence. These findings provide new insights into how astrocyte subtypes in the postnatal human brain may contribute to neuronal development and circuit formation during critical developmental periods, and offer clues to the potential origins of neurodevelopmental disorders.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• geo:GSE204684, at NCBI GEO; found in “Data availability and preprocessing”

Data availability and preprocessing

Human brain single-nucleus RNA-seq (snRNA-seq) data of the prefrontal cortex (PFC) were obtained from the public database of the Lister lab [25] and used to examine differentially expressed genes (DEGs), cell–cell communication, and regulon comparisons across lifespan stages. Only genes that were expressed in more than 10 cells were considered. Notably, despite considerable variations in cell numbers across stages, we were able to detect a minimum of 9,000 genes at each stage. Single-cell RNA-seq (scRNA-seq) data of the human cerebral cortex were obtained from the Gene Expression Omnibus (GEO) database (GSE204684 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE204684) [26]) and used to validate the developmental dynamics in the number of DEGs, as well as to investigate cell–cell communication and regulon comparisons. Bulk RNA-seq data of the human PFC were obtained from PsychENCODE [27] and used to infer cell-type composition across developmental stages, allowing us to examine potential changes in cellular composition during development. Adult human brain snRNA-seq data of the PFC were obtained from the public database [28] and were used to further assess the reliability of astrocyte subtype annotations.

Mouse scRNA-seq datasets of the cerebral cortex during development were obtained from the GEO database (GSE153164 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE153164) [29] and GSE204759 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE204759) [30]) and used for comparative analysis with human data on cell–cell communication and regulon comparisons. Additionally, a mouse scRNA-seq dataset of visual cortex development, obtained from the public database of the Zeng lab [31], was used to validate cross-species cell–cell communication and regulon comparisons. Genes detected in more than 10 cells were retained for subsequent analyses. We were able to detect a minimum of 10,000 genes at each stage.

Before performing the cross-species analysis, we conducted orthologous gene mapping and identified 13,447 shared orthologous genes across species.

Proteomics data were sourced from the Kriegstein lab [32]. The raw spatial transcriptome data of the human cerebral cortex generated in this study were obtained from the Genome Sequence Archive under accession code HRA004425.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 2, 28 September 2026

• Funding: added National Natural Science Foundation of China: 32570650

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 2 authors, 85 references.

Cite

This paper

Zhao, M., & Zhu, Y. (2026). The Role of Astrocyte-Neuron Interactions in Shaping Neuronal Maturation during Human Brain Development. Computational and structural biotechnology journal, 2026issue-1(1), 0083. https://doi.org/10.34133/csbj.0083

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