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PLCG2 Regulates Divergent Microglial Functions via TREM2-Dependent and -Independent Signaling

ABSTRACT: We use genetically engineered human iPSC-derived microglia-like cells (iMG) to show that TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, and lipid metabolism following myelin challenge. Loss of TREM2 or PLCγ2 signaling leads to a shared signature of transcriptional dysregulation that underlies these phenotypes. However, PLCγ2 also signals downstream of Toll-like receptors to mediate inflammatory responses in a TREM2-independent manner. Therefore, PLCγ2 activity regulates divergent microglial functions via distinct TREM2-dependent and -independent signaling and may be involved in the transition to a microglial state associated with neurodegenerative disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE144120 | GEO | 2020/05/24

REPOSITORIES: GEO

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PLCG2 Regulates Divergent Microglial Functions via TREM2-Dependent and -Independent Signaling

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