| First Author | Monzón-Sandoval J | Year | 2022 |
| Journal | Dis Model Mech | Volume | 15 |
| Issue | 10 | PubMed ID | 36254682 |
| Mgi Jnum | J:330956 | Mgi Id | MGI:7380504 |
| Doi | 10.1242/dmm.049349 | Citation | Monzon-Sandoval J, et al. (2022) Lipopolysaccharide distinctively alters human microglia transcriptomes to resemble microglia from Alzheimer's disease mouse models. Dis Model Mech 15(10):dmm049349 |
| abstractText | Alzheimer's disease (AD) is the most common form of dementia, and risk-influencing genetics implicates microglia and neuroimmunity in the pathogenesis of AD. Induced pluripotent stem cell (iPSC)-derived microglia (iPSC-microglia) are increasingly used as a model of AD, but the relevance of historical immune stimuli to model AD is unclear. We performed a detailed cross-comparison over time on the effects of combinatory stimulation of iPSC-microglia, and in particular their relevance to AD. We used single-cell RNA sequencing to measure the transcriptional response of iPSC-microglia after 24 h and 48 h of stimulation with prostaglandin E2 (PGE2) or lipopolysaccharide (LPS)+interferon gamma (IFN-gamma), either alone or in combination with ATPgammaS. We observed a shared core transcriptional response of iPSC-microglia to ATPgammaS and to LPS+IFN-gamma, suggestive of a convergent mechanism of action. Across all conditions, we observed a significant overlap, although directional inconsistency to genes that change their expression levels in human microglia from AD patients. Using a data-led approach, we identify a common axis of transcriptomic change across AD genetic mouse models of microglia and show that only LPS provokes a transcriptional response along this axis in mouse microglia and LPS+IFN-gamma in human iPSC-microglia. This article has an associated First Person interview with the first author of the paper. |
