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Series GSE235987 Query DataSets for GSE235987
Status Public on Jun 26, 2024
Title Enhancer-AAVs allow genetic access to diverse populations of astrocytes and oligodendrocytes across species
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Proper brain function requires the assembly and function of diverse populations of neurons and glia. Single cell gene expression studies have mostly focused on characterization of neuronal cell diversity; however, recent studies have revealed substantial diversity of glial cells, particularly astrocytes. To better understand glial cell types and their roles in neurobiology, we built a new suite of adeno-associated viral (AAV)-based genetic tools to enable genetic access to astrocytes and oligodendrocytes. These oligodendrocyte and astrocyte enhancer-AAVs were highly specific, showed variable expression levels, and our astrocyte enhancer-AAVs showed multiple distinct expression patterns that reflected the spatial distribution of astrocyte subtypes. To provide the best glial-specific functional tools, several enhancer-AAVs were: optimized for higher expression levels, shown to be functional and specific in rat and macaque, shown to maintain specific activity in epilepsy where traditional promoters changed activity, and used to drive functional transgenes in astrocytes including Cre recombinase and acetylcholine-responsive sensor iAChSnFR. The astrocyte-specific iAChSnFR revealed a clear reward-dependent acetylcholine response in astrocytes of the nucleus accumbens during reinforcement learning. Together, this collection of glial enhancer-AAVs will enable characterization of astrocyte and oligodendrocyte populations and their roles across species, disease states, and behavioral epochs.
 
Overall design Single-cell RNA-seq on flow-sorted enhancer-AAV-labeled transgene-expressing cells from 47 mouse brains. For each mouse brain up to 48 individual cells were profiled by SMARTer single-cell RNA-seq.
 
Contributor(s) Mich JK, Sunil S, Johansen N, Martinez RA, Leytze M, Gore BB, Mahoney JT, Ben-Simon Y, Bishaw Y, Omstead V, Campos J, Canfield R, Casper T, Dee N, Monet D, Gary A, Gibson S, Goldy J, Reding M, Opitz-Araya X, Groce EL, Sedeño-Cortés AE, Shapovalova NV, Taormina M, Taskin N, Tieu M, Valera Cuevas NJ, Weed N, Way S, Yao Z, McMillen DA, Kunst M, McGraw M, Thyagarajan B, Waters J, Bakken TE, Yao S, Smith KA, Svoboda K, Podgorski K, Kojima Y, Horwitz GD, Zeng H, Daigle TL, Lein ES, Tasic B, Ting JT, Levi BP
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Submission date Jun 27, 2023
Last update date Jun 26, 2024
Contact name John Kenneth Mich
E-mail(s) johnmi@alleninstitute.org
Organization name Allen Institute for Brain Science
Street address 615 Westlake Ave N
City Seattle
State/province WA
ZIP/Postal code 91878
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (2040)
GSM7512690 BrainCell_Enhancer-eHGT_374m_MouseID-614201_Cell-1
GSM7512691 BrainCell_Enhancer-3xCore2(390m)_MouseID-651223_Cell-1
GSM7512692 BrainCell_Enhancer-eHGT_405m_MouseID-601542_Cell-1
Relations
BioProject PRJNA988135

Download family Format
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE235987_mouse_2040scRNAseq_CellXGeneMtx_230626.tsv.gz 33.6 Mb (ftp)(http) TSV
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Raw data are available in SRA
Processed data are available on Series record

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