SHIP1 modulation and proteome characterization of microglia

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• Microglial function is critical in aging and neurodegenerative diseases like Alzheimer's.
• Genes like INPP5D (SHIP1) and TREM2 influence microglial roles in Alzheimer's disease.
• Understanding microglial states is essential for therapeutic development.

Purpose of the Study:

• To comprehensively examine microglia-like cells and primary microglia using proteome and transcriptome analyses.
• To elucidate the roles of INPP5D (SHIP1) and its encoded proteins in different microglial cell states.
• To compare commonly used in vitro microglia models (BV2, HMC3) with primary mouse microglia.

Main Methods:

• Proteomic and transcriptomic profiling of wildtype and INPP5D (SHIP1) knockout primary mouse microglia.
• Comparative proteomic and transcriptomic analysis of BV2, HMC3, and primary mouse microglia.
• Targeted lipidomic analysis of phosphatidylinositol (PI) species in HMC3 and BV2 cells.

Main Results:

• Homozygous SHIP1 knockout significantly altered the primary microglial proteome.
• BV2 cells showed proteomic similarity to primary mouse microglia, unlike human HMC3 cells.
• SHIP1 directly impacts phosphatidylinositol species, key targets identified in HMC3 and BV2 cells.

Conclusions:

• This omics analysis provides a systematic understanding of microglial models and function.
• Findings highlight SHIP1's significant role in microglial proteome regulation.
• The study enhances comprehension of microglial function in neurodegenerative diseases and potential therapeutics.