Microglia integration into midbrain organoids: Origin matters
- 1Amsterdam UMC
Abstract
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.
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BibTeX
@misc{verkerke2026microglia,
title = {{Microglia integration into midbrain organoids: Origin matters}},
author = {M. Verkerke and A. S. Guaqueta and S. Zekri and A.-M. v. Dam and H. E. de Vries and V. Donega},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.22.753683},
url = {https://www.biorxiv.org/content/10.64898/2026.09.22.753683v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Microglia integration into midbrain organoids: Origin matters
AU - M. Verkerke
AU - A. S. Guaqueta
AU - S. Zekri
AU - A.-M. v. Dam
AU - H. E. de Vries
AU - V. Donega
PY - 2026
DA - 2026/09/22
PB - bioRxiv
DO - 10.64898/2026.09.22.753683
UR - https://www.biorxiv.org/content/10.64898/2026.09.22.753683v1
AB - 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.
ER -