PLX189796

GSE147495: IL-33-PU.1 transcriptome reprogramming drives functional state transition and clearance activity of microglia in Alzheimers disease

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Impairment of microglial clearance activity contributes to beta-amyloid (A) pathology in Alzheimer disease (AD). While the transcriptome profile of microglia directs microglial functions, how the microglial transcriptome can be regulated to alleviate AD pathology is largely unknown. Here, we show that injection of interleukin (IL)-33 in an AD transgenic mouse model ameliorates A pathology by reprogramming microglial epigenetic and transcriptomic profiles to induce a microglial subpopulation with enhanced phagocytic activity. These IL-33responsive microglia (IL-33RM) express distinct transcriptome signature, highlighted by major histocompatibility complex class II genes, and restored homeostatic signature genes. IL-33induced remodeling of chromatin accessibility and PU.1 transcription factor binding at the signature genes of IL-33RM control their transcriptome reprogramming. Specifically, disrupting PU.1DNA interaction abolishes the microglial state transition and A clearance induced by IL-33. Thus, we define a PU.1-dependent transcriptional pathway that drives the IL-33induced functional state transition of microglia, resulting in enhanced A clearance. SOURCE: Nancy Ip (iplabgenetics@gmail.com) - Hong Kong University of Science and Technology