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Stem Cell Res. 2019 Jan;34:101360. doi: 10.1016/j.scr.2018.101360. Epub 2018 Nov 30.

Generation of a heterozygous p53 R249S mutant human embryonic stem cell line by TALEN-mediated genome editing.

Author information

1
Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China.
2
Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Department of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China.
3
Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
4
Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China.
5
Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, PR China.
6
Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; The University of Texas, MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
7
Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Guangdong Research Center of Metabolic Diseases of Integrated Western and Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
8
Women's Health Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
9
Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
10
Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China. Electronic address: xiaohp@mail.sysu.edu.cn.
11
Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Electronic address: ruiying.zhao@uth.tmc.edu.

Abstract

As one of the most essential genome guardians, p53 and its mutants have been suggested associated with many types of cancers. Many p53 mutants function induce unique phenotypes, including carcinogenesis, metastasis, and drug resistance. The p53(R249S) mutation is the most prevalent and specific mutation associated with liver cancer development. Here, we demonstrate the generation of a heterozygous p53(R249S) mutation in the H9 human embryonic stem cell line using TALEN-mediated genome editing. The generated cell line maintains a normal karyotype, a pluripotent state and the in vivo capacity to develop a teratoma containing all three germ layer tissues.

PMID:
30640060
DOI:
10.1016/j.scr.2018.101360
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