Lastly, we were excited to find that regions with increased chromatin accessibility in APOE2 microglia were enriched for vitamin D receptor binding, suggesting vitamin D signalling as a potential protective mechanism and therapeutic avenue.

6/n

Comparison with independent studies showed that APOE2 microglia were enriched for plaque-phagocytosing genes, prompting us to test their phagocytic activity. Using E. coli and myelin, we found that they were indeed more phagocytic than APOE4 microglia.

5/n

Genes downregulated in APOE4-expressing microglia were enriched in putatively protective microglial states, suggesting a failure to transition into these states.

Additionally, cytokine expression was elevated, consistent with previous findings in mouse microglia expressing APOE4.

4/n

We observed consistent differences in gene expression and chromatin accessibility. For example, the cellular migration-related gene CHCHD2 showed higher expression and increased chromatin accessibility near its transcription start site in APOE2 microglia.

3/n

As anticipated, the most pronounced differences were observed between APOE4 (risk-increasing in some populations) and APOE2 (protective).

Expression changes were partly driven by loss of function, but only genes downregulated in APOE4 and KO microglia were enriched for AD risk variants.

2/n

Excited to share that a chapter of my PhD has just been published in Nature Communications!

We profiled the transcriptomic and chromatin landscapes of microglia expressing the different APOE variants, which were xenografted into the brains of an Alzheimer's disease (AD) mouse model 🧠🧬

1/n

And just like that, 5 years in the Marzi lab @sj-marzi.bsky.social have come to an end. Couldn’t have asked for a better team ✨

Super excited to say, I’m switching fields and will be working with ancient human genomes in the Skov lab @lauritsskov.bsky.social in Copenhagen 🇩🇰