|
| Status |
Public on Jun 20, 2020 |
| Title |
In Vivo Chimeric Alzheimer’s Disease Modeling of Apolipoprotein E4 Toxicity in Human Neurons |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Despite its clear impact on Alzheimer’s Disease (AD) risk, apolipoprotein (apo) E4’s contributions to AD etiology remain poorly understood. Progress in answering this and other questions in AD research has been limited by an inability to model human-specific phenotypes in an in vivo environment. Here we transplanted human induced pluripotent stem cell (hiPSC)-derived neurons carrying normal apoE3 or pathogenic apoE4 into human apoE3 or apoE4 knock-in mouse hippocampi, enabling us to disentangle the effects of apoE4 produced in human neurons and in the brain environment. Using single nucleus RNA-sequencing (snRNA-seq), we identified key transcriptional changes specific to human neuron subtypes in response to endogenous or exogenous apoE4. We also found that Aβ from transplanted human neurons formed plaque-like aggregates, with differences in localization and interaction with microglia depending on the transplant and host apoE genotype. These findings highlight the power of in vivo chimeric disease modeling for studying AD.
|
| |
|
| Overall design |
Single-cell RNA Sequencing data from human induced pluripotent stem cell (hIPSC) derived neurons. hIPSC-derived neurons have an APOE4 genotype or are isogenic wth an APOE3 genotype. hIPSC-derived neurons were transplanted into and matured for 7 months in human APOE4-KI or human APOE3-KI mice.
|
| |
|
| Contributor(s) |
Najm R, Zalocusky K, Hao Y, Huang Y |
| Citation(s) |
32726626 |
| Submission date |
Jun 19, 2020 |
| Last update date |
Aug 24, 2020 |
| Contact name |
Kelly Zalocusky |
| Organization name |
Gladstone Institutes
|
| Street address |
1650 Owens Street, Gladstone Center for Translational Advancement
|
| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94158 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL25526 |
Illumina NovaSeq 6000 (Homo sapiens; Mus musculus) |
|
| Samples (4)
|
|
| Relations |
| BioProject |
PRJNA640668 |
| SRA |
SRP268072 |
Less...
More...