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Series GSE185472 Query DataSets for GSE185472
Status Public on Jan 16, 2024
Title Morphological diversification and functional maturation of human astrocytes in glia-enriched cortical organoids transplanted in the mouse brain
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Astrocytes, the most abundant glial cell type in the brain, are underrepresented in traditional cortical organoid models due to the delayed onset of cortical gliogenesis. Here, we introduce a novel glia-enriched cortical organoid model that exhibits accelerated astrogliogenesis. We demonstrated that induction of a gliogenic switch in a subset of progenitors enabled rapid derivation of astroglial cells, which account for 25-31% of the cell population within eight to ten weeks of differentiation. Intracerebral transplantation of these organoids reliably generated a diverse repertoire of cortical neurons and anatomical subclasses of human astrocytes. Spatial transcriptome profiling identified layer-specific expression patterns among distinct subclasses of astrocytes within the organoid transplants. Using an in vivo acute neuroinflammation model, we identified a subpopulation of astrocytes that rapidly activates proinflammatory pathways upon cytokine stimulation. Additionally, we demonstrated that CD38 signaling plays a crucial role in mediating metabolic and mitochondrial stress in reactive astrocytes. This model provides a robust platform for investigating human astrocyte function.
 
Overall design Single-nucleus RNA-Seq
Single-cell RNA-Seq
 
Contributor(s) Wang M, Shokhirev MN, Yu J, Gage FH, Zhang L
Citation(s) 38418648
Submission date Oct 06, 2021
Last update date Apr 16, 2024
Contact name April Elizabeth Williams
E-mail(s) apriljack06@gmail.com, awilliams@salk.edu
Phone 7345461645
Organization name Salk Institute for Biological Studies
Department IGC
Street address 10010 N Torrey Pines Rd
City San Diego
State/province California
ZIP/Postal code 92037
Country USA
 
Platforms (2)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (12)
GSM5615952 iPSC822_6m_transplant, snRNAseq
GSM5615953 Hues6_6m_transplant, snRNAseq
GSM6679384 Hues6_5m_transplant, snRNAseq
Relations
BioProject PRJNA769136
SRA SRP340289

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE185472_RAW.tar 628.0 Mb (http)(custom) TAR (of MTX, TAR, TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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