We identified PBX3 as an example of a TF that is closely linked to the inhibitory neuron lineage priming. In silico perturbation experiments of multimodal GRNs suggest PBX3 as a potential mediator of the effect. 🧬🔑


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Our findings show that chronic GC exposure alters lineage specification, with a selective priming of the inhibitory neuron lineage. 🧠


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In our study, we looked at how chronic GC exposure affects neural differentiation and lineage specification in human neural organoids, using single-cell techniques to map the molecular changes in detail. 🔬🧬

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Disease Modeling 😷 : Our atlas can be leveraged as a diverse control cohort to contextualise organoid models of disease, helping identify underlying genes and pathways. We found that comprehensive control data is vital for disentangling disease from regional effects.

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Quantifying Organoid Fidelity 📊: By estimating the transcriptomic similarity between primary and organoid brain counterparts, we provide a robust framework for assessing protocol variation and fidelity across labs and methods. Cell stress seems to be quite dependent on protocol.

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Identifying Missing Cell States 🔍: We map neural organoid cell types and states to a developing human brain reference, highlighting gaps in the diversity of brain regions present in current in vitro models. ⚠️While the telencephalon seems well-captured, this is not true for all brain regions.

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Introducing the Human Neural Organoid Cell Atlas 🗺️: We’ve integrated 36 neural organoid datasets across 26 protocols. This produced a comprehensive, integrated reference atlas, including a hierarchical cell-type annotation, partially derived by mapping to primary human 🧠.


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