 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Feb 16, 2021 |
| Title |
Control (healthy) iPSC-derived astrocytes treated with: Media (control) or aSYN F110 10uM |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
The overall goal was to identify changes in gene expression following treatment with aSYN F110 compared to control (untreated).
Alpha-synuclein (αSYN) protein has been observed in reactive astrocytes in PD patients’ brains, raising the question of how αSYN, neuroinflammation, and astrocytes interact in PD pathogenesis. Here, we examined the cellular changes triggered by tumor necrosis factor alpha (TNFα) and different αSYN species in astrocytes derived from induced pluripotent stem cells. Human astrocytes treated with TNFα displayed a strong reactive pro-inflammatory phenotype with upregulation of pro-inflammatory gene networks, activation of the NF-kB pathway, and release of pro-inflammatory cytokines, whereas those treated with high molecular weight αSYN fibrils acquired a reactive antigen (cross-)presenting phenotype with upregulation of MHC genes and increased HLA-DR/DQ/DP and HLA-F molecules at the cell surface. Surprisingly, cell surface location of MHC proteins was abrogated by larger F110 fibrils polymorph, despite the upregulation of MHC genes. A proteomics investigation further confirmed a direct interaction between astrocytic MHC proteins and αSYN fibril peptides. Interestingly, TNFα and αSYN fibrils competed to drive the astrocyte immune reactive response. The astrocyte immune responses were accompanied by an impaired ATP-generating mitochondrial respiration, which was exacerbated in PD astrocytes containing a PARK2-variant. Our data provide evidence for astrocytic involvement in PD pathogenesis and reveal their complex immune reactive responses to exogenous stressors.
|
| |
|
| Overall design |
4 samples were analyzed per condition from 2 different donors: 2 different differentations of 37R were used and 9A and 36D samples were the same donor reprogrammed using retro or sendai virus, respectively.
|
| |
|
| Contributor(s) |
Russ K, Teku G, Bousset L, Redeker V, Piel S, Savchenko E, Savistchenko J, Stummann TC, Azevedo C, Collin A, Goldwurm S, Fog K, Elmer E, Vihinen M, Melki R, Roybon L |
| Citation(s) |
33761362 |
| Submission date |
Feb 15, 2021 |
| Last update date |
Apr 01, 2021 |
| Contact name |
Laurent Roybon |
| E-mail(s) |
laurent.roybon@med.lu.se
|
| Phone |
+46462229833
|
| Organization name |
Lund University
|
| Department |
Experimental Medical Science
|
| Lab |
CSC lab
|
| Street address |
Solvegatan 19
|
| City |
Lund |
| ZIP/Postal code |
221 84 |
| Country |
Sweden |
| |
|
| Platforms (1) |
| GPL23159 |
[Clariom_S_Human] Affymetrix Clariom S Assay, Human (Includes Pico Assay) |
|
| Samples (8)
|
|
| This SubSeries is part of SuperSeries: |
| GSE166771 |
TNFα and α-synuclein fibrils differently regulate human astrocyte immune reactivity and impair mitochondrial respiration |
|
| Relations |
| BioProject |
PRJNA701929 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE166769_RAW.tar |
8.6 Mb |
(http)(custom) |
TAR (of CEL) |
| GSE166769_Russ_et_al_Table_S2_Affymetrix_Cell_Reports.xlsx |
13.4 Mb |
(ftp)(http) |
XLSX |
| Processed data included within Sample table |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...