@article {Sun2023-ti,
	title = {Human microglial state dynamics in Alzheimer{\textquoteright}s disease progression},
	journal = {Cell},
	volume = {186},
	number = {20},
	year = {2023},
	pages = {4386{\textendash}4403.e29},
	abstract = {Summary Altered microglial states affect neuroinflammation, neurodegeneration, and disease but remain poorly understood. Here, we report 194,000 single-nucleus microglial transcriptomes and epigenomes across 443 human subjects and diverse Alzheimer{\textquoteright}s disease (AD) pathological phenotypes. We annotate 12 microglial transcriptional states, including AD-dysregulated homeostatic, inflammatory, and lipid-processing states. We identify 1,542 AD-differentially-expressed genes, including both microglia-state-specific and disease-stage-specific alterations. By integrating epigenomic, transcriptomic, and motif information, we infer upstream regulators of microglial cell states, gene-regulatory networks, enhancer-gene links, and transcription-factor-driven microglial state transitions. We demonstrate that ectopic expression of our predicted homeostatic-state activators induces homeostatic features in human iPSC-derived microglia-like cells, while inhibiting activators of inflammation can block inflammatory progression. Lastly, we pinpoint the expression of AD-risk genes in microglial states and differential expression of AD-risk genes and their regulators during AD progression. Overall, we provide insights underlying microglial states, including state-specific and AD-stage-specific microglial alterations at unprecedented resolution.},
	keywords = {Alzheimer{\textquoteright}s, cell states, disease-stage response, inflammation, iPSCs, microglia, single-cell, transcription factors},
	author = {Sun, Na and Victor, Matheus B and Park, Yongjin P and Xiong, Xushen and Scannail, Aine Ni and Leary, Noelle and Prosper, Shaniah and Viswanathan, Soujanya and Luna, Xochitl and Boix, Carles A and James, Benjamin T and Tanigawa, Yosuke and Galani, Kyriaki and Mathys, Hansruedi and Jiang, Xueqiao and Ng, Ayesha P and Bennett, David A and Tsai, Li-Huei and Kellis, Manolis}
}
