 |
 |
GEO help: Mouse over screen elements for information. |
|
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 |
Sep 13, 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)
|
|
Relations |
BioProject |
PRJNA769136 |
SRA |
SRP340289 |
Supplementary file |
Size |
Download |
File type/resource |
GSE185472_10wOrg_withAnnot.txt.gz |
97.4 Kb |
(ftp)(http) |
TXT |
GSE185472_RAW.tar |
628.0 Mb |
(http)(custom) |
TAR (of MTX, TAR, TSV) |
GSE185472_integratedorganoid_withAnnot.txt.gz |
423.0 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
|
|
|
|
 |