Stem-cell-derived human microglia transplanted in mouse brain to study human disease
Stem-cell-derived human microglia transplanted in mouse brain to study human disease
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DOI：
10.1038/s41593-019-0525-x
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发表时间：
2019-12-01
影响因子：
25
通讯作者：
De Strooper, Bart
中科院分区：
文献类型：
--
作者：
Mancuso, Renzo;Van den Daele, Johanna;De Strooper, Bart
尽管遗传学强调了小胶质细胞在阿尔茨海默病中的作用，但三分之一的推定阿尔茨海默病风险基因缺乏足够的小鼠直系同源物。在这里，我们成功地将来自胚胎干细胞的人类小胶质细胞移植到小鼠大脑中。这些细胞在转录上再现了离体人类初级小胶质细胞，并显示出人类特异性阿尔茨海默病风险基因的表达。寡聚淀粉样蛋白-β诱导人类与小鼠小胶质细胞的不同反应。该模型可用于研究小胶质细胞在神经系统疾病中的作用。
Although genetics highlights the role of microglia in Alzheimer's disease, one-third of putative Alzheimer's disease risk genes lack adequate mouse orthologs. Here we successfully engraft human microglia derived from embryonic stem cells in the mouse brain. The cells recapitulate transcriptionally human primary microglia ex vivo and show expression of human-specific Alzheimer's disease risk genes. Oligomeric amyloid-beta induces a divergent response in human versus mouse microglia. This model can be used to study the role of microglia in neurological diseases.