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Spatiotemporal molecular and cellular dynamics of intratelencephalic neurons in mouse prefrontal cortex during postnatal development

ABSTRACT: In early postnatal brain, the prefrontal cortex (PFC) remains immature and highly plastic, particularly for the intratelencephalic (IT) neurons. However, the spatiotemporal molecular and cellular dynamics of PFC during this period remain poorly characterized. Here, we performed spatiotemporal single-cell RNA analysis on mouse PFC during different postnatal time points and systematically delineated the molecular and cellular dynamics of mouse PFC during early postnatal development, among which IT neurons exhibit most dramatic alterations. Based on these comprehensive spatiotemporal atlases of PFC, we deciphered the time-specific molecular and cellular characteristics during the maturation process of IT neurons in PFC, particularly the dynamic expression programs of genes regulating axon development and synaptic formation, and the risk genes of neurological developmental diseases. Furthermore, we revealed the dynamic neuron-glia interaction patterns and the underlying signaling pathways during early postnatal period. Our study provided a comprehensive resource and important insights for PFC development and PFC-associated neurological diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE298260 | GEO | 2025/05/28

REPOSITORIES: GEO

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Project description:Astrocytes are the most abundant glial cell type in the central nervous system (CNS). Most astrocytes are born during the early postnatal period in the rodent brain and mature alongside neurons, demonstrating remarkable morphological structural complexity, attaining maturity in the second postnatal month. Across the remainder of the lifespan astrocytes participate in CNS homeostasis, support neuronal partners, and contribute to nearly all aspects of CNS functioning. In the present study, we analyzed astrocyte gene expression in rodent wild type cortex across the lifespan (7 days to 18 months). A pairwise timepoint comparison of differential gene expression during early development and CNS maturation (7 days – 60 days) revealed four unique astrocyte gene clusters, each with hundreds of genes and demonstrating a unique temporal profile. These clusters distinctively related to cell division, cell morphology, Astrocytes are the most abundant glial cell type in the central nervous system (CNS). Astrocytes are born during the early postnatal period in the rodent brain and mature alongside neurons, demonstrate remarkable morphological structural complexity which is attained in the second postnatal month. Throughout this period of development and across the remainder of the lifespan, astrocytes participate in CNS homeostasis, support neuronal partners, and contribute to nearly all aspects of CNS function. In the present study, we analyzed astrocyte gene expression in the cortex of wild-type rodents throughout their lifespan (postnatal 7 days to 18 months). A pairwise timepoint comparison of differential gene expression during early development and CNS maturation (7 days–60 days) revealed four unique astrocyte gene clusters, each with hundreds of genes, and which demonstrate unique temporal profiles. These clusters are distinctively related to cell division, cell morphology, cellular communication and vascular structure and regulation. A similar analysis across adulthood and in the aging brain (3 months to 18 months) identified similar patterns of grouped gene expression related to cell metabolism and cell structure. Additionally, our analysis identified that during the aging process astrocytes demonstrate a bias toward shorter transcripts, with loss of longer genes related to synapse development and a significant increase in shorter transcripts related to immune regulation and the response to DNA damage. Our study highlights the critical role that astrocytes play in maintaining CNS function throughout life, and reveals molecular shifts that occur during development and aging.

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Spatiotemporal molecular and cellular dynamics of intratelencephalic neurons in mouse prefrontal cortex during postnatal development

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