A Transcriptome Database for Astrocytes, Neurons, and Oligodendrocytes: A New Resource for Understanding Brain Development and Function

By John D. Cahoy, B. Emery, Amit Kaushal, L. Foo, Jennifer L Zamanian, K. S. Christopherson, Yi Xing, J. Lubischer, P. Krieg, S. Krupenko and 2 more. Journal of Neuroscience, 2008

3,030 citations recorded by the source corpus.

Understanding the cell–cell interactions that control CNS development and function has long been limited by the lack of methods to cleanly separate neural cell types. Here we describe methods for the prospective isolation and purification of astrocytes, neurons, and oligodendrocytes from developing and mature mouse forebrain. We used FACS (fluorescent-activated cell sorting) to isolate astrocytes from transgenic mice that express enhanced green fluorescent protein (EGFP) under the control of an S100β promoter. Using Affymetrix GeneChip Arrays, we then created a transcriptome database of the expression levels of >20,000 genes by gene profiling these three main CNS neural cell types at various postnatal ages between postnatal day 1 (P1) and P30. This database provides a detailed global characterization and comparison of the genes expressed by acutely isolated astrocytes, neurons, and oligodendrocytes. We found that Aldh1L1 is a highly specific antigenic marker for astrocytes with a substantially broader pattern of astrocyte expression than the traditional astrocyte marker GFAP. Astrocytes were enriched in specific metabolic and lipid synthetic pathways, as well as the draper/Megf10 and Mertk/integrin αvβ5 phagocytic pathways suggesting that astrocytes are professional phagocytes. Our findings call into question the concept of a “glial” cell class as the gene profiles of astrocytes and oligodendrocytes are as dissimilar to each other as they are to neurons. This transcriptome database of acutely isolated purified 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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/434b04e80c2165344d16805c23b9d6af77e8379a

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Citations in the corpus

Functional organization of the transcriptome in human brain (2008, background): “To test this hypothesis, we cross-referenced genes that serve as markers for specific cell classes in the adult mouse brai”
Gene discovery and polygenic prediction from a 1.1-million-person GWAS of educational attainment (2018, methodology): “These annotations are in turn based on the expression data gathered from postnatal mice brains by Cahoy et al.(53) We will provide more details”
Origin of new glial cells in intact and injured adult spinal cord. (2010, background): “White matter astrocytes expressed Sox9 and high levels of GFAP, but not Olig2.”
Molecular Identity of Human Outer Radial Glia During Cortical Development (2015, neutral): “See also Figure S6. genes are also associated with astrocytes later in development, including TNC, ITGB5, DIO2, and ACSBG1 (Cahoy et al., 2008), and LIFR signaling through STAT3 can promote gliogenesis in combination with BMP signaling (Bonaguidi et al., 2005).”
Sweet Sixteen for ANLS (2012, background): “…isolated cells (Hydén and Lange, 1962; Hamberger and Hydén, 1963) up to most recent transcriptomic studies (Rossner et al, 2006; Lovatt et al, 2007; Cahoy et al, 2008), all argue for a predominance of glycolytic and glycogen pathways in astrocytes and of lactate utilization in neurons.”
Regulation of synaptic connectivity by glia (2010, background): “Recent gene-expression analysis of astrocytes in vivo showed that astrocytes produce messenger RNAs that encode several synaptic adhesion proteins, such as neurexins, neuroligins and cadherin”
Astrocytes and disease: a neurodevelopmental perspective. (2012, background): “Recently, the application of gene expression profiling to purified astrocyte populations (Cahoy et al. 2008; Doyle et al. 2008; Fu et al. 2009; Rowitch and Kriegstein 2010) has revealed several potential new markers, such as the gene encoding the folate metabolic enzyme Aldh1L1 (Anthony and Heintz 2”
An integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR and NF1 (2010, methodology): “To gain insight into the biological meaning of the subtypes, we used data from the brain transcriptome database presented by Cahoy et al. (2008) to define gene sets associated with neurons, oligodendrocytes, astrocytes, and cultured astroglial cells.”