Microglia integration into midbrain organoids – origin matters
Microglia integration into midbrain organoids – origin matters
Publication status: preprint
A plain-language reading has not been prepared for this paper yet.
Original abstract
Summary Midbrain organoids (MOs) can be powerful tools to study brain diseases, yet one shortcoming is the lack of microglia due to their mesodermal developmental origin. Previous studies have incorporated iPSC-derived microglia (iMG), but their immature phenotype restricts the applicability to model age-related neuroinflammatory processes relevant to diseases such as Parkinson’s Disease (PD). To address this, we have incorporated MOs with human postmortem PD microglia, iPSC-derived microglial progenitors (iMP), and iMG. Postmortem microglia had a higher infiltration capacity resulting in more microglia per organoid, while iMP had a higher migration capacity reaching the core of the organoid. Compared to iPSC-derived cells, more infiltrated postmortem PD microglia were HLA Class II positive and CD68 positive. This novel approach of integrating postmortem microglia into organoids opens new avenues for modelling age-related neuroinflammatory diseases. Ongoing methodological advancements like our study will offer the field a valuable tool for studying human microglia biology in both health and disease. Highlights Postmortem microglia have a higher infiltration capacity resulting in more microglia per organoid iPSC-derived microglial progenitors could have a higher migration capacity to reach the organoid core More postmortem microglia express HLA Class II and CD68 than iPSC-derived cells P2RY12 and IBA1 expression is higher in iPSC-derived microglial progenitors eTOC Verkerke and colleagues explore a novel approach of integrating postmortem microglia from Parkinson’s Disease donors into midbrain organoids. Comparison to integration of iPSC-derived microglia and microglial progenitors reveals a higher infiltration capacity of postmortem microglia with an elevated presence of inflammatory markers HLA Class II and CD68. This innovative approach paves the way for new insights into age-related neuroinflammatory processes using organoid models.