iPSC-derived microglia for research of Alzheimer's disease
Company 2021
F. Hoffmann-La Roche Ltd., Basel, Switzerland
Microglia are key in the homeostatic well-being of the brain and microglial dysfunction has been implicated in neurodegenerative disorders such as Alzheimer’s disease (AD). Due to the many limitations to study microglia in situ or isolated for large scale drug discovery applications, there is a high need to develop robust and scalable human cellular models of microglia.
Here, the optimization of a protocol to generate microglia from iPSCs in a monoculture condition is presented. The study explores whether these cells can serve as a model to study microglial function and gene expression in the context of TREM2 modulation. TREM2 is a risk gene for AD and an important regulator of microglia. As a major distinction from previously published co-culture methods, in iPSC-generated microglia from monoculture, an increased TREM2 mRNA expression was observed. The regulatory function of TREM2 in these cells was confirmed by comparing wild type with isogenic TREM2 knock-out iPSC microglia. The overall approach resulted in a workstream to generate human iPSC microglia by a directed and neuronal co-culture independent differentiation, resulting in distinct phenotypes for mechanistic studies in AD. This iPSC microglia protocol can now be applied to scale up the production of these cells, study certain AD-related disease settings, and perform compound screening and mechanistic experiments in drug development.
Alzheimer’s risk gene TREM2 determines functional properties of new type of human iPSC-derived microglia
Markus Britschgi, Simon Gutbier
Added on: 05-11-2021
[1] https://www.frontiersin.org/articles/10.3389/fimmu.2020.617860/full
