文章基本信息

标题：A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation
本地全文：下载
作者：Katarina Bartalska ; Verena Hübschmann ; Medina Korkut-Demirbaş 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：7
页码：1-31
DOI：10.1016/j.isci.2022.104580
语种：English
出版社：Elsevier
摘要：SummaryCerebral 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.Graphical abstractDisplay OmittedHighlights•Microglia-like cells occur alongside retinal cups in unguided hIPSC differentiation•They populate non-pigmented 3D-cystic compartments•The cystic compartment has a mesenchymal identity, which sequesters microglia•Microglia-like cells adapt a BAM signature in cystic compartmentsMicroglia-like cells occur alongside human iPSC-derived retinal organoid differentiation and preferentially occupy the mesenchymal region.