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. 2023 Mar 6;28(12):5077–5089. doi: 10.1038/s41380-023-01997-1

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 6 — In the DFOs, RG cells express IL6ST and are, therefore, capable of responding to Hyper-IL-6 treatment. IL6ST activation results in phosphorylation of Y705-STAT3 and elevated number of vRGs without an effect on the IPCs and dExNs numbers at days 50–55 of organoid differentiation. Downstream, immune response-related gene expression is activated while protein translation gene expression is downregulated in vRGs. Hyper-IL-6 treatment results in cell type-independent upregulation of NR2F1. The protracted effects of Hyper-IL-6 treatment (day 90 of organoid differentiation) include increased number of uExNs and laminar mislocalization of both dExNs and uExNs.