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Temporal profiling of male cortical astrocyte transcription predicts molecular shifts from early development to aging

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE272573 | GEO | 2025/03/24

REPOSITORIES: GEO

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Project description:A Transcriptome Database for Astrocytes, Neurons, and Oligodendrocytes: A New Resource for Understanding Brain Development and Function Understanding the cell-cell interactions that control CNS development and function has long been limited by the lack of methods to cleanly separate astrocytes, neurons, and oligodendrocytes. Here we describe the first method for the isolation and purification of developing and mature astrocytes from mouse forebrain. This method takes advantage of the expression of S100β by astrocytes. We used fluorescent activated cell sorting (FACS) to isolate EGFP positive cells from transgenic mice that express EGFP under the control of an S100β promoter. By depletion of astrocytes and oligodendrocytes we obtained purified populations of neurons, while by panning with oligodendrocyte-specific antibodies we obtained purified populations of oligodendrocytes. Using GeneChip Arrays we then created a transcriptome database of the expression levels of over 20,000 genes by gene profiling these three main CNS neural cell types at postnatal ages day 1 to 30. This database provides the first global characterization of the genes expressed by mammalian astrocytes in vivo and is the first direct comparison between the astrocyte, neuron, and oligodendrocyte transcriptomes. We demonstrate that Aldh1L1, a highly expressed astrocyte gene, is a highly specific antigenic marker for astrocytes with a substantially broader, and therefore potentially more useful, pattern of astrocyte expression than the traditional astrocyte marker GFAP. This transcriptome database of acutely isolated and highly pure populations of astrocytes, neurons and oligodendrocytes provides a resource to the neuroscience community by providing improved cell type specific markers and for better understanding of neural development, function, and disease. We acutely purified mouse astrocytes from early postnatal ages (P1) to later postnatal ages (P30), when astrocyte differentiation is morphologically complete (Bushong et al., 2004), and acutely purified mouse OL-lineage cells from stages ranging from OPCs to newly differentiated OLs to myelinating OLs. We extracted RNA from each of these highly purified, acutely isolated cell types and used GeneChip Arrays to determine the expression levels of over 20,000 genes and construct a comprehensive database of cell type specific gene expression in the mouse forebrain. Analysis of this database confirms cell type specific expression of many well characterized and functionally important genes. In addition, we have identified thousands of new cell type enriched genes, thereby providing important new information about astrocyte, OL, and neuron interactions, metabolism, development, and function. This database provides a comparison of the genome-wide transcriptional profiles of the main CNS cell types and is a resource to the neuroscience community for better understanding the development, physiology, and pathology of the CNS. Keywords: Developmental CNS Cell type comparision

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Temporal profiling of male cortical astrocyte transcription predicts molecular shifts from early development to aging

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