RESUMO
The DNA helicase RECQL4 is known for its roles in DNA replication and repair. RECQL4 mutations cause several genetic disorders including Rothmund-Thomson syndrome (RTS), characterized by developmental defects and predisposition to osteosarcoma. Here we reprogrammed fibroblasts with a heterozygous RECQL4 mutation (c.1878â¯+â¯32_1878â¯+â¯55del24) to induced pluripotent stem cells (iPSCs). These iPSCs are pluripotent and are able to be differentiated into all three germ layers, providing a novel tool to further interrogate the role of RECQL4 DNA helicase in vitro.
Assuntos
Células-Tronco Pluripotentes Induzidas/metabolismo , RecQ Helicases/genética , Adulto , Feminino , Heterozigoto , Humanos , Mutação , Adulto JovemRESUMO
The tumor suppressor gene TP53 is the most frequently mutated gene in human cancers. Many hot-spot mutations of TP53 confer novel functions not found in wild-type p53 and contribute to tumor development and progression. We report on the generation of a H1 human embryonic stem cell line carrying a homozygous TP53 R282W mutation using TALEN-mediated genome editing. The generated cell line demonstrates normal karyotype, maintains a pluripotent state, and is capable of generating a teratoma in vivo containing tissues from all three germ layers.
Assuntos
Edição de Genes/métodos , Células-Tronco Embrionárias Humanas/metabolismo , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição/metabolismo , Proteína Supressora de Tumor p53/genética , Homozigoto , Humanos , Masculino , Mutação/genética , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição/genéticaRESUMO
Genetic mutations in TP53 contribute to multiple human cancers. Here we report the generation of a H1-p53(R248W/R248W) human embryonic stem cell line harboring a homozygous TP53 R248W mutation created by TALEN-mediated precise gene editing. The H1-p53(R248W/R248W) cell line maintains a normal karyotype, robust pluripotency gene expression, and the potential to differentiate to the three germ layers.