RNA-seq of B16F10 lung metastases derived from APOE2 and APOE3 mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA860792 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR20339665.fastq.gz | Fastqsanger.gz | |||
| SRR20339666.fastq.gz | Fastqsanger.gz | |||
| SRR20339667.fastq.gz | Fastqsanger.gz | |||
| SRR20339668.fastq.gz | Fastqsanger.gz | |||
| SRR20339669.fastq.gz | Fastqsanger.gz |
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Project description:In 12-month-old APOE targeted-replacement mice, we report that overall differences in gene expression were the most prominent when comparing the protective APOE2 to the other two alleles, with fewer differences found when comparing the risk-neutral APOE3 and disease-promoting APOE4 alleles. When compared with either APOE3 or APOE4, differential expression of genes within the endosomal pathways is a prominent feature of APOE2 expression in the brain. We hypothesized that the protective effects of APOE2 are mediated through the endosomal pathway during aging. In contrast to Alzheimer’s disease and APOE4 models, we detected normal morphology and abundance of early endosomes within cortical neurons of APOE2 targeted-replacement mice during aging despite decreased rab5b recruitment to early endosomes. Similarly, the morphology and abundance of retromer-associated vesicles was normal in APOE2 mice, despite reduced recruitment of vesicle-associated VPS35. Significantly, we observed increased brain extracellular levels of endosome-derived exosomes in APOE2 compared with APOE3 mice during aging, indicative of an enhanced endosomal cargo clearance to the extracellular space that contributes to a homeostatic balance of endosomal functions. Our findings thus demonstrate that APOE2 effectively offsets endosomal pathway changes during aging to preserve its integrity by enhancing exosome biogenesis, mitigating age-driven endosomal dysfunction that contributes to Alzheimer’s disease risk.
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