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Na Sun, Matheus B. Victor, Yongjin Park, Xushen Xiong, Aine Ni Scannail, Noelle Leary, Shaniah Prosper, Soujanya Viswanathan, Xochitl Luna, Carles A. Boix and 9 more
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'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.
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Sun, N., Victor, M. B., Park, Y., Xiong, X., Scannail, A. N., Leary, N., Prosper, S., Viswanathan, S., Luna, X., Boix, C. A., James, B. T., Tanigawa, Y., Galani, K., Mathys, H., Jiang, X., Ng, A. P., Bennett, D. A., Tsai, L., & Kellis, M. (2023). Human microglial state dynamics in Alzheimer’s disease progression. Cell, 186(20), 4386–4403.e29. https://doi.org/10.1016/j.cell.2023.08.037
Sun, Na, et al. "Human microglial state dynamics in Alzheimer’s disease progression." Cell, vol. 186, no. 20, 2023, pp. 4386–4403.e29, https://doi.org/10.1016/j.cell.2023.08.037.
Sun, Na, Matheus B. Victor, Yongjin Park, Xushen Xiong, Aine Ni Scannail, Noelle Leary, Shaniah Prosper, et al. "Human microglial state dynamics in Alzheimer’s disease progression." Cell 186, no. 20 (2023): 4386–4403.e29. https://doi.org/10.1016/j.cell.2023.08.037.
Sun N., Victor M. B., Park Y. [и др.] Human microglial state dynamics in Alzheimer’s disease progression // Cell. — 2023. — Vol. 186, № 20. — P. 4386–4403.e29. — URL: https://doi.org/10.1016/j.cell.2023.08.037
@article{sun2023human,
title = {{Human microglial state dynamics in Alzheimer’s disease progression}},
author = {Na Sun and Matheus B. Victor and Yongjin Park and Xushen Xiong and Aine Ni Scannail and Noelle Leary and Shaniah Prosper and Soujanya Viswanathan and Xochitl Luna and Carles A. Boix and Benjamin T. James and Yosuke Tanigawa and Kyriaki Galani and Hansruedi Mathys and Xueqiao Jiang and Ayesha P. Ng and David Alan Bennett and Li‐Huei Tsai and M Kellis},
journal = {Cell},
year = {2023},
volume = {186},
number = {20},
pages = {4386--4403.e29},
doi = {10.1016/j.cell.2023.08.037},
url = {https://doi.org/10.1016/j.cell.2023.08.037}
}TY - JOUR AU - Sun, Na AU - Victor, Matheus B. AU - Park, Yongjin AU - Xiong, Xushen AU - Scannail, Aine Ni AU - Leary, Noelle AU - Prosper, Shaniah AU - Viswanathan, Soujanya AU - Luna, Xochitl AU - Boix, Carles A. AU - James, Benjamin T. AU - Tanigawa, Yosuke AU - Galani, Kyriaki AU - Mathys, Hansruedi AU - Jiang, Xueqiao AU - Ng, Ayesha P. AU - Bennett, David Alan AU - Tsai, Li‐Huei AU - Kellis, M TI - Human microglial state dynamics in Alzheimer’s disease progression JO - Cell VL - 186 IS - 20 SP - 4386 EP - 4403.e29 PY - 2023 DA - 2023/09/01 DO - 10.1016/j.cell.2023.08.037 UR - https://doi.org/10.1016/j.cell.2023.08.037 ER -
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