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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. 1 — a IL-6 has two receptors, IL6R and IL6ST. When both of them are expressed in the target cell, the IL-6-dependent signaling cascade is called “classic” whereas when IL6R is provided extracellularly for example by a different cell in its soluble form, the cascade is called “trans”. b Hyper-IL-6 is a chimeric protein consisting of soluble IL6R (s-IL6R) and IL-6 connected to each other through a peptide linker. c Upon binding to IL6R and IL-6, IL6ST induces phosphorylation of JAK1, which in turn phosphorylates STAT3 at Y705. Then, p-Y705-STAT3 enters the nucleus and activates transcription. d In the developing human neocortex, IL6R is expressed exclusively in microglia whereas IL6STexpression can be detected in radial glia (RG) and to a lesser extent in intermediate progenitor cells (IPC), as well as in glial cells in a neocortical scRNAseq dataset (Nowakowski et al., Science, 2017). e, f IL6ST (magenta) immunofluorescence of human PCW13 neocortex, shows protein expression in the ventricular zone (VZ, e) and subventricular zone (SVZ, f) where it is associated with the marker of RGs Nestin (green). g IL6ST immunofluorescence is associated with Nestin in the VZ-like area of dorsal forebrain organoids (DFO) at day 50 of differentiation. h IL6ST (magenta) in human neocortex at PCW12 is weakly associated with PPP1R17 (green) which is used as a marker of IPCs. i, IL6ST immunofluorescence is weakly associated with PPP1R17 in DFOs at day 55 of differentiation. For e–i, the images represent maximum intensity projections of z-stacks sampled in 337 nm steps. The lines in the insets represent the positions from which orthogonal sections were sampled. Orthogonal sections for separate channels are shown underneath the respective inset images.