@article{11478, 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.}, author = {Bartalska, Katarina and Hübschmann, Verena and Korkut, Medina and Cubero, Ryan J and Venturino, Alessandro and Rössler, Karl and Czech, Thomas and Siegert, Sandra}, issn = {2589-0042}, journal = {iScience}, number = {7}, publisher = {Elsevier}, title = {{A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation}}, doi = {10.1016/j.isci.2022.104580}, volume = {25}, year = {2022}, } @article{6412, abstract = {Polycomb group (PcG) proteins play critical roles in the epigenetic inheritance of cell fate. The Polycomb Repressive Complexes PRC1 and PRC2 catalyse distinct chromatin modifications to enforce gene silencing, but how transcriptional repression is propagated through mitotic cell divisions remains a key unresolved question. Using reversible tethering of PcG proteins to ectopic sites in mouse embryonic stem cells, here we show that PRC1 can trigger transcriptional repression and Polycomb-dependent chromatin modifications. We find that canonical PRC1 (cPRC1), but not variant PRC1, maintains gene silencing through cell division upon reversal of tethering. Propagation of gene repression is sustained by cis-acting histone modifications, PRC2-mediated H3K27me3 and cPRC1-mediated H2AK119ub1, promoting a sequence-independent feedback mechanism for PcG protein recruitment. Thus, the distinct PRC1 complexes present in vertebrates can differentially regulate epigenetic maintenance of gene silencing, potentially enabling dynamic heritable responses to complex stimuli. Our findings reveal how PcG repression is potentially inherited in vertebrates.}, author = {Moussa, Hagar F. and Bsteh, Daniel and Yelagandula, Ramesh and Pribitzer, Carina and Stecher, Karin and Bartalska, Katarina and Michetti, Luca and Wang, Jingkui and Zepeda-Martinez, Jorge A. and Elling, Ulrich and Stuckey, Jacob I. and James, Lindsey I. and Frye, Stephen V. and Bell, Oliver}, issn = {20411723}, journal = {Nature Communications}, number = {1}, publisher = {Springer Nature}, title = {{Canonical PRC1 controls sequence-independent propagation of Polycomb-mediated gene silencing}}, doi = {10.1038/s41467-019-09628-6}, volume = {10}, year = {2019}, }