| Literature DB >> 31768052 |
Alexandra Grubman1,2,3, Gabriel Chew4, John F Ouyang4, Guizhi Sun1,2,3, Xin Yi Choo1,2,3,5, Catriona McLean6, Rebecca K Simmons7,8, Sam Buckberry7,8, Dulce B Vargas-Landin7,8, Daniel Poppe7,8, Jahnvi Pflueger7,8, Ryan Lister7,8, Owen J L Rackham9, Enrico Petretto10, Jose M Polo11,12,13.
Abstract
There is currently little information available about how individual cell types contribute to Alzheimer's disease. Here we applied single-nucleus RNA sequencing to entorhinal cortex samples from control and Alzheimer's disease brains (n = 6 per group), yielding a total of 13,214 high-quality nuclei. We detail cell-type-specific gene expression patterns, unveiling how transcriptional changes in specific cell subpopulations are associated with Alzheimer's disease. We report that the Alzheimer's disease risk gene APOE is specifically repressed in Alzheimer's disease oligodendrocyte progenitor cells and astrocyte subpopulations and upregulated in an Alzheimer's disease-specific microglial subopulation. Integrating transcription factor regulatory modules with Alzheimer's disease risk loci revealed drivers of cell-type-specific state transitions towards Alzheimer's disease. For example, transcription factor EB, a master regulator of lysosomal function, regulates multiple disease genes in a specific Alzheimer's disease astrocyte subpopulation. These results provide insights into the coordinated control of Alzheimer's disease risk genes and their cell-type-specific contribution to disease susceptibility. These results are available at http://adsn.ddnetbio.com.Entities:
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Year: 2019 PMID： 31768052 DOI： 10.1038/s41593-019-0539-4
Source DB: PubMed Journal: Nat Neurosci ISSN： 1097-6256 Impact factor: 24.884