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| Status |
Public on Nov 25, 2022 |
| Title |
TDP-43 condensates and lipid droplets regulate the reactivity of microglia and regeneration after traumatic brain injury |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Decreasing the activation of pathology-activated microglia is crucial to prevent chronic inflammation and tissue scarring. In this study, we used a stab wound injury model in zebrafish and identified an injury-induced microglial state characterized by the accumulation of lipid droplets and TAR DNA-binding protein of 43 kDa (TDP-43)+ condensates. Granulin-mediated clearance of both lipid droplets and TDP-43+ condensates was necessary and sufficient to promote the return of microglia back to the basal state and achieve scarless regeneration. Moreover, in postmortem cortical brain tissues from patients with traumatic brain injury, the extent of microglial activation correlated with the accumulation of lipid droplets and TDP-43+ condensates. Together, our results reveal a mechanism required for restoring microglia to a nonactivated state after injury, which has potential for new therapeutic applications in humans.
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| Overall design |
Single-cell RNA sequencing of telencephalic cells from wildtype (Wt) and grna-/-;grnb-/- (Mutant) animals. Intact, 3 days post injury (dpi) and 7 dpi are used as time points. Animals were from 3 to 5 months old.
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| Contributor(s) |
Zambusi A, Novoselc KT, Hutten S, Kalpazidou S, Koupourtidou C, Schieweck R, Aschenbroich S, Silva L, Yazgili AS, Bebber Fv, Schmid B, Möller G, Tritscher C, Stigloher C, Delbridge C, Sirko S, Günes ZI, Liebscher S, Schlegel J, Aliee H, Theis F, Meiners S, Kiebler M, Dormann D, Ninkovic J |
| Citation(s) |
36424432 |
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| Submission date |
Jun 29, 2021 |
| Last update date |
Feb 24, 2023 |
| Contact name |
Jovica Ninkovic |
| E-mail(s) |
jovica.ninkovic@helmholtz-munich.de
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| Organization name |
LMU München
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| Department |
Department for Cell Biology
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| Street address |
Großhaderner Straße 9
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| City |
Planegg-Martinsried |
| State/province |
Bayern |
| ZIP/Postal code |
82152 |
| Country |
Germany |
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| Platforms (1) |
| GPL24995 |
Illumina NovaSeq 6000 (Danio rerio) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA742394 |
| SRA |
SRP326122 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE179134_RAW.tar |
614.4 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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