Ouissame Filali (United States of America)
FujiFilm Cellular Dynamics, Inc.
Sales
Ouissame Filali joined FUJIFILM Cellular Dynamics Inc. (FCDI) in 2016 and is currently a Field Application Scientist responsible for the Central Europe territory. She provides on-site and remote high-level technical application support, product demonstrations and training, and tackles customer concerns optimally through in-depth troubleshooting. In collaboration with the Sales team, Ouissame supports the organization in the achievement of the regional commercial goals. She is responsible of building effective relationships with new and existing clients for field application purposes, monitoring the feedback on product usage and experience, and assisting the researcher in developing scientifically accurate applications. Prior to joining FCDI, Ouissame was a post-doc at The university of Montreal and the Vrije Universiteit in Amsterdam. Ouissame has a Ph.D. in Neurosciences from Université Claude Bernard Lyon 1.

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 Conference Calendar

COMPARATIVE ANALYSIS OF CRYOPRESERVED ISOGENIC IPSCS DERIVED I TREM2 WT, ENGINEERED TREM2HZ, TREM2 HO AND DONOR-DERIVED R47H MICROGLIA FROM FOR DISEASE MODELLING APPLICATIONS

Session Name
0390 - MICROGLIA, TREM2, NEUROINFLAMMATION (ID 87)
Session Type
SYMPOSIUM
Date
Wed, 16.03.2022
Session Time
04:15 PM - 06:00 PM
Room
ONSITE: 113
Lecture Time
05:00 PM - 05:15 PM
Presenter

Abstract

Aims

Recent GWAS have shown that sequence variants in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) are associated with an increased risk for AD. TREM2 senses lipids and mediates myelin phagocytosis. Loss-of-function (LOF) variants of TREM2, have been associated with an increased amyloid plaque seeding, reduced amyloid clustering and impairment of Microglia function. Cryopreserved microglia from engineered and patient derived iPSC provide an in vitro tool to model complex interactions to mimic neurogenerative diseases (Abud et al. 2017).

Methods

Episomally reprogrammed iPSCs were subjected to nuclease-mediated homologous recombination to generate TREM2 Heterozygous (TREM2HZ), homozygous iPSC line (TREM2HO) as well as R47H expressing donor derived Microglia. Parental, TREM2 HZ, TREM2 HO and R47H iPSCs were differentiated to microglia under defined conditions.

Results

Comparative analysis of TREM2HZ, TREM2HO and WT isogenic microglia identified different pathways altered by partial or complete loss of TREM2 function. TREM2HZ displayed enhanced down-regulation of SREBF2, the master regulator of cholesterol biosynthesis resulting in a decrease in the cholesterol and fatty acid synthesis, coinciding with increased lipid efflux. The role of TREM2 on the downregulation of in Gas6/Axl axis, Siglec11 expression, GPCRs, ion channels, transport proteins, soluble TREM2, neuroinflammatory cytokines and chemokines, phagocytic function to amyloid beta and a direct link between TREM2 with COMT, NRXN2 and SST expression is critical to understand the role of TREM2 in the onset of AD.

Conclusions

iPSC-derived microglia with TREM2 variants co-cultured with astrocyte and neurons can be used to mimic the onset of AD in a dish.

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