A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation


Cerebral organoids differentiated from human-induced pluripotent stem cells (hiPSC) provide a unique opportunity to investigate brain development. However, organoids usually lack microglia, brain-resident immune cells, which are present in the early embryonic brain and participate in neuronal circuit development. Here, we find IBA1+ microglia-like cells alongside retinal cups between week 3 and 4 in 2.5D culture with an unguided retinal organoid differentiation protocol. Microglia do not infiltrate the neuroectoderm and instead enrich within non-pigmented, 3D-cystic compartments that develop in parallel to the 3D-retinal organoids. When we guide the retinal organoid differentiation with low-dosed BMP4, we prevent cup development and enhance microglia and 3D-cysts formation. Mass spectrometry identifies these 3D-cysts to express mesenchymal and epithelial markers. We confirmed this microglia-preferred environment also within the unguided protocol, providing insight into microglial behavior and migration and offer a model to study how they enter and distribute within the human brain. © 2022 The Author(s).

Authors Bartalska K, Hübschmann V, Korkut-Demirbaş M, Cubero RJA, Venturino A, Rössler K, Czech T, Siegert S
Journal iScience
Publication Date 2022 Jul 15;25(7):104580
PubMed 35789843
PubMed Central PMC9250027
DOI 10.1016/j.isci.2022.104580

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