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

Bartalska, Katarina; Hübschmann, Verena; Korkut, Medina; Cubero, Ryan J; Venturino, Alessandro; Rössler, Karl; Czech, Thomas; Siegert, Sandra

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

Bartalska K, Hübschmann V, Korkut M, Cubero RJ, Venturino A, Rössler K, Czech T, Siegert S. 2022. A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation. iScience. 25(7), 104580.

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DOI

10.1016/j.isci.2022.104580

Journal Article | Published | English

Scopus indexed

Author

Bartalska, Katarina^ISTA; Hübschmann, Verena^ISTA; Korkut, Medina^ISTA ; Cubero, Ryan John^ISTA ; Venturino, Alessandro^ISTA ; Rössler, Karl; Czech, Thomas; Siegert, Sandra^ISTA

Department

Siegert Group

Grant

Microglia action towards neuronal circuit formation and function in health and disease
IST Austria Open Access Fund
How human microglia shape developing neurons during health and inflammation

Abstract

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.

Publishing Year

2022

Date Published

2022-07-15

Journal Title

iScience

Acknowledgement

We thank the scientific service units at ISTA, specifically the lab support facility and imaging & optics facility for their support; Nicolas Armel for performing the Mass Spectrometry. We thank Alexandra Lang and Tanja Peilnsteiner for their help in human brain tissue collection, Rouven Schulz for his insights into the functional assays We thank all members of the Siegert group for constant feedback on the project and Margaret Maes, Rouven Schulz, and Marco Benevento for feedback on the manuscript. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant No. 715571 to S.S.) and from the Gesellschaft für Forschungsförderung Niederösterreich (grant No. Sc19-017 to V.H.).

Acknowledged SSUs

Imaging & Optics Facility
Lab Support Facility

Volume

Issue

Article Number

104580

eISSN

2589-0042

IST-REx-ID

11478

Cite this

Bartalska K, Hübschmann V, Korkut M, et al. A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation. iScience. 2022;25(7). doi:10.1016/j.isci.2022.104580

Bartalska, K., Hübschmann, V., Korkut, M., Cubero, R. J., Venturino, A., Rössler, K., … Siegert, S. (2022). A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation. IScience. Elsevier. https://doi.org/10.1016/j.isci.2022.104580

Bartalska, Katarina, Verena Hübschmann, Medina Korkut, Ryan J Cubero, Alessandro Venturino, Karl Rössler, Thomas Czech, and Sandra Siegert. “A Systematic Characterization of Microglia-like Cell Occurrence during Retinal Organoid Differentiation.” IScience. Elsevier, 2022. https://doi.org/10.1016/j.isci.2022.104580.

K. Bartalska et al., “A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation,” iScience, vol. 25, no. 7. Elsevier, 2022.

Bartalska, Katarina, et al. “A Systematic Characterization of Microglia-like Cell Occurrence during Retinal Organoid Differentiation.” IScience, vol. 25, no. 7, 104580, Elsevier, 2022, doi:10.1016/j.isci.2022.104580.

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