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. 2022 Oct 12;610(7931):319–326. doi: 10.1038/s41586-022-05277-w

Fig. 1. Transplantation of human cortical organoids in the developing rat cortex.

Fig. 1

a, Schematic of the experimental design. hCO generated from hiPS cells are transplanted at days 30–60 of differentiation into the S1 of newborn athymic rats. b, Coronal and horizontal view T2-weighted MRI images showing t-hCO in the S1 at 2 months post-transplantation. Scale bar, 2 mm. c, Quantification of the success rate of transplantations shown per hiPS cell line (n = 108, numbers inside bars indicate number of t-hCO per hIPS cell line) and cortical or subcortical position (n = 88). d, Coronal MRI images (left; scale bar, 3 mm) and corresponding 3D volume reconstructions (scale bar, 3 mm) showing t-hCO growth over 3 months. e, Overview of example t-hCOs in the rat cortex. Scale bar, 1 mm. f, Representative immunocytochemistry images of t-hCO showing from top left to right (at time in differentiation): PPP1R17 (4 months), NeuN (8 months), SOX9 and GFAP (8 months), PDGFRα; (8 months), MAP2 (8 months) and IBA1 (8 months). Scale bars, 20 μm. Co-expression of HNA indicates cells of human origin. g, snRNA-seq: uniform manifold approximation and projection (UMAP) dimensional reduction visualization of all clustered high-quality t-hCO nuclei after Seurat integration (n = 3 t-hCO samples, n = 2 hiPS cell lines). Astroglia, astrocyte lineage cells; cyc prog, cycling progenitor; GluN DL, deep layer glutamatergic neuron; GluN DL/SP, deep layer and subplate glutamatergic neuron; GluN UL, upper layer glutamatergic neuron; oligo, oligodendrocyte; OPC, oligodendrocyte progenitor cell; RELN, reelin neurons. h, Gene Ontology (GO) term enrichment analysis of genes significantly upregulated (adjusted P < 0.05, fold change > 2, expressed in at least 10% of nuclei) in t-hCO glutamatergic neurons compared with hCO glutamatergic neurons. The dashed line denotes a q value of 0.05. i, UMAP visualization of GluN cell types of t-hCO using label transfer from the adult human motor cortex22 snRNA-seq reference dataset. CT, corticothalamic cell; ET, extratelencephalic cell; IT, intratelencephalic cell; NP, near-projecting.