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Title: Transcriptional signature in microglia associated with A? plaque phagocytosis
Authors: Grubman, Alexandra
Choo, Xin Yi
Chew, Gabriel
Ouyang, John F. 
Sun, Guizhi
Croft, Nathan P.
Rossello, Fernando J.
Simmons, Rebecca
Buckberry, Sam
Landin, Dulce Vargas
Pflueger, Jahnvi
Vandekolk, Teresa H.
Abay, Zehra
Zhou, Yichen
Liu, Xiaodong
Chen, Joseph
Larcombe, Michael
Haynes, John M.
Mclean, Catriona
Williams, Sarah
Chai, Siew Yeen
Wilson, Trevor
Lister, Ryan
Pouton, Colin W.
Purcell, Anthony W.
Rackham, Owen J. L. 
Petretto, Enrico 
Polo, Jose M.
Issue Date: 21-May-2021
Publisher: Nature Research
Citation: Grubman, Alexandra, Choo, Xin Yi, Chew, Gabriel, Ouyang, John F., Sun, Guizhi, Croft, Nathan P., Rossello, Fernando J., Simmons, Rebecca, Buckberry, Sam, Landin, Dulce Vargas, Pflueger, Jahnvi, Vandekolk, Teresa H., Abay, Zehra, Zhou, Yichen, Liu, Xiaodong, Chen, Joseph, Larcombe, Michael, Haynes, John M., Mclean, Catriona, Williams, Sarah, Chai, Siew Yeen, Wilson, Trevor, Lister, Ryan, Pouton, Colin W., Purcell, Anthony W., Rackham, Owen J. L., Petretto, Enrico, Polo, Jose M. (2021-05-21). Transcriptional signature in microglia associated with A? plaque phagocytosis. Nature Communications 12 (1) : 3015. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: The role of microglia cells in Alzheimer’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 HIF1? 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. © 2021, The Author(s).
Source Title: Nature Communications
ISSN: 2041-1723
DOI: 10.1038/s41467-021-23111-1
Rights: Attribution 4.0 International
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