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SHIP1 modulation and proteome characterization of microglia.
Ahat, Erpan; Shi, Zanyu; Chu, Shaoyou; Bui, Hai Hoang; Mason, Emily R; Soni, Disha M; Roth, Kenneth D; Chalmers, Michael James; Oblak, Adrian L; Zhang, Jie; Gutierrez, Jesus A; Richardson, Timothy.
Afiliação
  • Ahat E; Eli Lilly and Company, Indianapolis, USA. Electronic address: ahat_erpan@lilly.com.
  • Shi Z; Department of Biostatistics & Health Data Science, Indiana University School of Medicine, Indianapolis, USA.
  • Chu S; Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, USA.
  • Bui HH; Eli Lilly and Company, Indianapolis, USA.
  • Mason ER; Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, USA.
  • Soni DM; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
  • Roth KD; Eli Lilly and Company, Indianapolis, USA.
  • Chalmers MJ; Eli Lilly and Company, Indianapolis, USA.
  • Oblak AL; Department of Radiology & Imaging Sciences, Indiana University School of Medicine, Indianapolis, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
  • Zhang J; Department of Biostatistics & Health Data Science, Indiana University School of Medicine, Indianapolis, USA.
  • Gutierrez JA; Eli Lilly and Company, Indianapolis, USA.
  • Richardson T; Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
J Proteomics ; 302: 105198, 2024 Jun 30.
Article em En | MEDLINE | ID: mdl-38777089
ABSTRACT
Understanding microglial states in the aging brain has become crucial, especially with the discovery of numerous Alzheimer's disease (AD) risk and protective variants in genes such as INPP5D and TREM2, which are essential to microglia function in AD. Here we present a thorough examination of microglia-like cells and primary mouse microglia at the proteome and transcriptome levels to illuminate the roles these genes and the proteins they encode play in various cell states. First, we compared the proteome profiles of wildtype and INPP5D (SHIP1) knockout primary microglia. Our findings revealed significant proteome alterations only in the homozygous SHIP1 knockout, revealing its impact on the microglial proteome. Additionally, we compared the proteome and transcriptome profiles of commonly used in vitro microglia BV2 and HMC3 cells with primary mouse microglia. Our results demonstrated a substantial similarity between the proteome of BV2 and mouse primary cells, while notable differences were observed between BV2 and human HMC3. Lastly, we conducted targeted lipidomic analysis to quantify different phosphatidylinositols (PIs) species, which are direct SHIP1 targets, in the HMC3 and BV2 cells. This in-depth omics analysis of both mouse and human microglia enhances our systematic understanding of these microglia models.

SIGNIFICANCE:

Given the growing urgency of comprehending microglial function in the context of neurodegenerative diseases and the substantial therapeutic implications associated with SHIP1 modulation, we firmly believe that our study, through a rigorous and comprehensive proteomics, transcriptomics and targeted lipidomic analysis of microglia, contributes to the systematic understanding of microglial function in the context of neurodegenerative diseases.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Microglia / Proteoma / Doença de Alzheimer / Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases Limite: Animals / Humans Idioma: En Revista: J Proteomics Assunto da revista: BIOQUIMICA Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Microglia / Proteoma / Doença de Alzheimer / Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases Limite: Animals / Humans Idioma: En Revista: J Proteomics Assunto da revista: BIOQUIMICA Ano de publicação: 2024 Tipo de documento: Article