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. 2021 Jul 27;12:4535. doi: 10.1038/s41467-021-24781-7

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© The Author(s) 2021

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. 4 — A, B Hematoxylin and eosin (H&E) staining of differentiated and undifferentiated patient retinoblastoma. C Unsupervised hierarchical clustering of retinoblastoma tumors showing separation of the differentiated and undifferentiated samples. D–F Copy number variation in the differentiated retinoblastomas (D) and undifferentiated patient retinoblastomas (F) and H&E staining (E) of a patient eye that has regions of both undifferentiated (region 1) and differentiated (region 2) tumor, suggesting intratumor cellular heterogeneity. G Copy number variation and clustering of the retinal organoid-derived tumors. H t-distributed stochastic neighbor embedding (tSNE) plot of the St. Jude retinoblastomas, retinal organoid-derived tumors, retinal organoids, and iPSC/ESCs integrated with the Molecular Neuropathology (MPN) database of brain regions and pediatric brain tumors. I tSNE plot of the boxed region in (H) showing clustering of the organoid-derived tumors with patient retinoblastomas. J tSNE plot of the patient, O-PDX, and organoid-derived retinoblastomas with iPSC/ESCs and normal retinal organoids. K tSNE plot of O-PDX and organoid-derived retinoblastomas with iPSC/ESCs and normal retinal organoids. Scale bars: 25 μm.