ОписTransplantation of human cortical organoids in the developing rat cortex.webp |
English: "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." |
Автор |
Authors of the study: Omer Revah, Felicity Gore, Kevin W. Kelley, Jimena Andersen, Noriaki Sakai, Xiaoyu Chen, Min-Yin Li, Fikri Birey, Xiao Yang, Nay L. Saw, Samuel W. Baker, Neal D. Amin, Shravanti Kulkarni, Rachana Mudipalli, Bianxiao Cui, Seiji Nishino, Gerald A. Grant, Juliet K. Knowles, Mehrdad Shamloo, John R. Huguenard, Karl Deisseroth & Sergiu P. Pașca |