@article{dfa715414a6a40edb521b6dad9d017b2,
title = "Transcriptional signature in microglia associated with Aβ plaque phagocytosis",
abstract = "The role of microglia cells in Alzheimer{\textquoteright}s disease (AD) is well recognized, however their molecular and functional diversity remain unclear. Here, we isolated amyloid plaque-containing (using labelling with methoxy-XO4, XO4+) and non-containing (XO4−) microglia from an AD mouse model. Transcriptomics analysis identified different transcriptional trajectories in ageing and AD mice. XO4+ microglial transcriptomes demonstrated dysregulated expression of genes associated with late onset AD. We further showed that the transcriptional program associated with XO4+ microglia from mice is present in a subset of human microglia isolated from brains of individuals with AD. XO4− microglia displayed transcriptional signatures associated with accelerated ageing and contained more intracellular post-synaptic material than XO4+ microglia, despite reduced active synaptosome phagocytosis. We identified HIF1α as potentially regulating synaptosome phagocytosis in vitro using primary human microglia, and BV2 mouse microglial cells. Together, these findings provide insight into molecular mechanisms underpinning the functional diversity of microglia in AD.",
author = "Alexandra Grubman and Choo, {Xin Yi} and Gabriel Chew and Ouyang, {John F.} and Guizhi Sun and Croft, {Nathan P.} and Rossello, {Fernando J.} and Rebecca Simmons and Sam Buckberry and Landin, {Dulce Vargas} and Jahnvi Pflueger and Vandekolk, {Teresa H.} and Zehra Abay and Yichen Zhou and Xiaodong Liu and Joseph Chen and Michael Larcombe and Haynes, {John M.} and Catriona McLean and Sarah Williams and Chai, {Siew Yeen} and Trevor Wilson and Ryan Lister and Pouton, {Colin W.} and Purcell, {Anthony W.} and Rackham, {Owen J.L.} and Enrico Petretto and Polo, {Jose M.}",
note = "Funding Information: The authors acknowledge Flowcore, Monash Micro Imaging, Monash Health Translation Precinct Medical Genomics Facility, Micromon, Monash Histology Platform and Australian Research Laboratories/Monash Animal Research Platform, Monash University, for the provision of instrumentation, training and technical support. We thank Dr. Steve Chai and Genevieve Buckley for their expertise with Imaris, Angela Vais for her advice regarding tissue sections, Dr. Steven Firth for provision of confocal imaging expertise. We also thank Prof. Peter Crack for providing BV2 cells and Dr. Anja Knaupp for mCherry control lentiviruses. We thank Dr. Gurpreet Kaur (10X Genomics) for her insight regarding single-cell sequencing analysis. We thank Kirill Tsyganov for a pipeline for mapping bulk RNA-seq data and Tony Grubman for assistance with coding. The Australian Regenerative Medicine Institute is supported by grants from the State Government of Victoria and the Australian Government. A.G was funded by a NHMRC-ARC Dementia Fellowship and Dementia Australia Research Foundation Grant and funding from Yulgilbar Foundation and Dementia Australia. J.M.P. was funded by a Sylvia-Charles Viertel Fellowship. J.M.P., C.P., J.H. and A.G. received a Monash University JMP Grant and A.G. received a Monash University Platform Access Grant. Part of this work was funded by a Monash Network of Excellence grant. G.S. was funded by the Yulgilbar Foundation. Publisher Copyright: {\textcopyright} 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = dec,
doi = "10.1038/s41467-021-23111-1",
language = "English",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}
