Alzheimer's disease-induced phagocytic microglia express a specific profile of coding and non-coding RNAs

阿尔茨海默病诱导的吞噬性小胶质细胞表达特定的编码和非编码 RNA

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作者:Flavia Scoyni, Luca Giudice, Mari-Anna Väänänen, Nicholas Downes, Paula Korhonen, Xin Yi Choo, Nelli-Noora Välimäki, Petri Mäkinen, Nea Korvenlaita, Annemieke J Rozemuller, Helga E de Vries, Jose Polo, Tiia A Turunen, Seppo Ylä-Herttuala, Thomas B Hansen, Alexandra Grubman, Minna U Kaikkonen, Tarja

Discussion

Our study pinpoints key regulators of microglial Aβ clearing capacity suggesting new targets for future therapeutic approaches.

Methods

We isolated Aβ-laden microglia from the brain of 5xFAD mice for RNA sequencing to characterize the transcriptional signature in phagocytic microglia and to identify the key non-coding RNAs capable of regulating microglial phagocytosis. Through spatial sequencing, we show the transcriptional changes of microglia in the AD mouse brain in relation to Aβ proximity.

Results

Finally, we show that phagocytic messenger RNAs are regulated by miR-7a-5p, miR-29a-3p and miR-146a-5p microRNAs and segregate the DAM population into phagocytic and non-phagocytic states.

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