 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Sep 20, 2018 |
| Title |
TREM2 haploinsufficiency impairs microglia’s response to injury and exacerbates tau pathology in a tauopathy mouse model [RNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Alzheimer's disease (AD), the most common form of dementia, is characterized by the abnormal accumulation of amyloid plaques and hyperphosphorylated tau aggregates, as well as microgliosis. The link between mutations in Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), a microglia-expressed gene, and the increased risk for developing late-onset AD suggests a detrimental role for microglia in disease pathophyioslogy. Hemizygous TREM2 mutations are posited to increase risk for AD through loss-of-function haploinsufficiency. The effects of TREM2 haploinsufficiency on tau pathology and tau-associated deficits have not yet been characterized. Using in vivo imaging, we showed that TREM2 haploinsufficiency, but not complete loss of TREM2, resulted in a striking agedependent impairment in microglia’s response to injury without affecting baseline motility. This TREM2-dependent effect on microglial motility is consistent with transcriptomic alterations in cell motility uncovered with unbiased RNAsequencing analysis. Moreover, TREM2 haploinsufficiency, but not complete loss of TREM2, exacerbated phosphorylated tau pathology in transgenic mice expressing mutant human tau. In addition, TREM2 haploinsufficiency increased tau inclusions and tau-mediated inflammation without further exacerbating neuronal loss. Our findings demonstrate for the first time that TREM2 haploinsufficiency induces deficits in a tauopathy mouse model, supporting the notion that the hemizygous missense variant results in loss-of-function.
|
| |
|
| Overall design |
Adult microglia were isolated from 3-5 month old TREM2+/+, TREM2+/- and TREM2-/- mice using CD11b magnetic beads, followed by total RNA isolation using an RNeasy kit (Qiagen).
|
| |
|
| Contributor(s) |
Sayed FA, Telpoukhovskaia M, Li Y, Zhou Y, Le D, Hauduc A, Ludwig C, Gao F, Clelland C, Zhan L, Davalos D, Akassoglou K, Coppola G, Gan L |
| Citation(s) |
30232263 |
| |
| Submission date |
Nov 23, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Giovanni Coppola |
| E-mail(s) |
gcoppola@ucla.edu
|
| Phone |
310-794-4172
|
| Organization name |
UCLA
|
| Department |
Psychiatry and Neurology
|
| Lab |
Neurogenetics
|
| Street address |
1524 Gonda, 695 Charles Young Drive South
|
| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
|
| Samples (10)
|
|
| This SubSeries is part of SuperSeries: |
| GSE118630 |
Differential Effects of Partial and Complete Loss of TREM2 on Microglial Injury Response and Tauopathy |
|
| Relations |
| BioProject |
PRJNA419639 |
| SRA |
SRP125551 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE107293_RAW.tar |
1.7 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
|
|
|
|
 |
Less...
More...