title: “Naive Induced Pluripotent Stem Cells Generated From beta-Thalassemia Fibroblasts Allow Efficient Gene Correction With CRISPR/Cas9” authors:

• Yang, Yuanyuan
• Zhang, Xiaobai
• Yi, Li
• Hou, Zhenzhen
• Chen, Jiayu, …
• Jiang, Cizhong
• Wang, Yixuan
• Gao, Shaorong

date: “2016-01-01T00:00:00Z” doi: “10.5966/sctm.2015-0157”

publishDate: “2016-01-01T00:00:00Z” publication_types: [“2”]

publication: “STEM CELLS TRANSLATIONAL MEDICINE” publication_short: "”

abstract: “Conventional primed human embryonic stem cells and induced pluripotent stem cells (iPSCs) exhibit molecular and biological characteristics distinct from pluripotent stem cells in the naive state. Although naive pluripotent stem cells show much higher levels of self-renewal ability and multidifferentiation capacity, it is unknown whether na ve iPSCs can be generated directly from patient somatic cells and will be superior to primed iPSCs. In the present study, we used an established 5i/L/FA system to directly reprogram fibroblasts of a patient with beta-thalassemia into transgene-free na ve iPSCs with molecular signatures of ground-state pluripotency. Furthermore, these na ve iPSCs can efficiently produce cross-species chimeras. Importantly, using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 nuclease genome editing system, these na ve iPSCs exhibit significantly improved gene-correction efficiencies compared with the corresponding primed iPSCs. Furthermore, human naive iPSCs could be directly generated from noninvasively collected urinary cells, which are easily acquired and thus represent an excellent cell resource for further clinical trials. Therefore, our findings demonstrate the feasibility and superiority of using patient-specific iPSCs in the naive state for disease modeling, gene editing, and future clinical therapy.”

summary: “Conventional primed human embryonic stem cells and induced pluripotent stem cells (iPSCs) exhibit molecular and biological characteristics distinct from pluripotent stem cells in the naive state. Although naive pluripotent stem cells show much higher levels of self-renewal ability and multidifferentiation capacity, it is unknown whether na ve iPSCs can be generated directly from patient somatic cells and will be superior to primed iPSCs. In the present study, we used an established 5i/L/FA system to directly reprogram fibroblasts of a patient with beta-thalassemia into transgene-free na ve iPSCs with molecular signatures of ground-state pluripotency. Furthermore, these na ve iPSCs can efficiently produce cross-species chimeras. Importantly, using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 nuclease genome editing system, these na ve iPSCs exhibit significantly improved gene-correction efficiencies compared with the corresponding primed iPSCs. Furthermore, human naive iPSCs could be directly generated from noninvasively collected urinary cells, which are easily acquired and thus represent an excellent cell resource for further clinical trials. Therefore, our findings demonstrate the feasibility and superiority of using patient-specific iPSCs in the naive state for disease modeling, gene editing, and future clinical therapy.”

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links:

• name: “PubMed” url: “https://pubmed.ncbi.nlm.nih.gov/26676643/" url_pdf: “publication/2016.stem_cells_translational_medicine.yang_yuanyuan/full.pdf”

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