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DOI | 10.1073/PNAS.2011780117 |
Human embryonic stem cell-derived organoid retinoblastoma reveals a cancerous origin | |
Liu H.; Zhang Y.; Zhang Y.-Y.; Li Y.-P.; Hua Z.-Q.; Zhang C.-J.; Wu K.-C.; Yu F.; Zhang Y.; Su J.; Jin Z.-B. | |
发表日期 | 2021 |
ISSN | 00278424 |
起始页码 | 33628 |
结束页码 | 33638 |
卷号 | 117期号:52 |
英文摘要 | Retinoblastoma (Rb) is the most prevalent intraocular malignancy in children, with a worldwide survival rate <30%. We have developed a cancerous model of Rb in retinal organoids derived from genetically engineered human embryonic stem cells (hESCs) with a biallelic mutagenesis of the RB1 gene. These organoid Rbs exhibit properties highly consistent with Rb tumorigenesis, transcriptome, and genome-wide methylation. Single-cell sequencing analysis suggests that Rb originated from ARR3-positive maturing cone precursors during development, which was further validated by immunostaining. Notably, we found that the PI3K-Akt pathway was aberrantly deregulated and its activator spleen tyrosine kinase (SYK) was significantly up-regulated. In addition, SYK inhibitors led to remarkable cell apoptosis in cancerous organoids. In conclusion, we have established an organoid Rb model derived from genetically engineered hESCs in a dish that has enabled us to trace the cell of origin and to test novel candidate therapeutic agents for human Rb, shedding light on the development and therapeutics of other malignancies. © 2020 National Academy of Sciences. All rights reserved. |
英文关键词 | Cell of origin; Human embryonic stem cells; RB1; Retinal organoids; Retinoblastoma |
语种 | 英语 |
scopus关键词 | retinoblastoma protein; transcriptome; amino acid sequence; animal; carcinogenesis; chemistry; genetics; human; human embryonic stem cell; metabolism; mutagenesis; mutation; nonobese diabetic mouse; nucleotide sequence; organoid; pathology; retinoblastoma; Amino Acid Sequence; Animals; Base Sequence; Carcinogenesis; Human Embryonic Stem Cells; Humans; Mice, Inbred NOD; Mutagenesis; Mutation; Organoids; Retinoblastoma; Retinoblastoma Protein; Transcriptome |
来源期刊 | Proceedings of the National Academy of Sciences of the United States of America
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文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/179671 |
作者单位 | Laboratory of Stem Cell and Retinal Regeneration, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; Institute of Biomedical Big Data, School of Biomedical Engineering, School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing, 100730, China; Institute of Stem Cell Research, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China |
推荐引用方式 GB/T 7714 | Liu H.,Zhang Y.,Zhang Y.-Y.,et al. Human embryonic stem cell-derived organoid retinoblastoma reveals a cancerous origin[J],2021,117(52). |
APA | Liu H..,Zhang Y..,Zhang Y.-Y..,Li Y.-P..,Hua Z.-Q..,...&Jin Z.-B..(2021).Human embryonic stem cell-derived organoid retinoblastoma reveals a cancerous origin.Proceedings of the National Academy of Sciences of the United States of America,117(52). |
MLA | Liu H.,et al."Human embryonic stem cell-derived organoid retinoblastoma reveals a cancerous origin".Proceedings of the National Academy of Sciences of the United States of America 117.52(2021). |
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