Human embryonic stem cell-derived organoid retinoblastoma reveals a cancerous origin
| Autor: | Chang-Jun Zhang, Yan-Ping Li, Kun-Chao Wu, Yaru Zhang, Hui Liu, Jianzhong Su, Zi-Qi Hua, Zi-Bing Jin, You-You Zhang, Yan Zhang, Fulong Yu |
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| Rok vydání: | 2020 |
| Předmět: |
retinal organoids
Carcinogenesis Cell of origin Human Embryonic Stem Cells Syk Biology medicine.disease_cause Retinoblastoma Protein Transcriptome Mice Inbred NOD Organoid medicine Animals Humans Amino Acid Sequence Multidisciplinary Base Sequence Retinoblastoma Biological Sciences cell of origin medicine.disease Embryonic stem cell Organoids Mutagenesis Mutation Cancer research RB1 Immunostaining Neuroscience |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.2011780117 |
| Popis: | Significance As a genetic malignancy, retinoblastoma (Rb) is caused by RB1 mutations; however, its developmental origin and drug agents for human Rb remain largely unexplored. Here we describe an innovative Rb organoid model derived from human embryonic stem cells with a biallelic mutagenesis of the RB1 gene. We identify tumorigenic growth in the Rb organoids, as well as properties consistent with human primary Rb. We confirm that the Rb cell of origin stemmed from ARR3+ maturing cone precursor cells and SYK inhibitors displaying a significant therapeutic response. Our elegant in-dish Rb organoid model can be used to efficiently and effectively dissect the origin of Rb and mechanisms of Rb tumorigenesis, as well as screen novel therapies. Retinoblastoma (Rb) is the most prevalent intraocular malignancy in children, with a worldwide survival rate |
| Databáze: | OpenAIRE |
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