A homozygous p53 R282W mutant human embryonic stem cell line generated using TALEN-mediated precise gene editing

Ruoji Zhou; An Xu; Donghui Wang; Dandan Zhu; Helen Mata; Zijun Huo; Jian Tu; Mo Liu; Alaa M T Mohamed; Brittany E Jewell; Julian Gingold; Weiya Xia; Pulivarthi H Rao; Mien-Chie Hung; Ruiying Zhao; Dung-Fang Lee

doi:10.1016/j.scr.2018.01.035

A homozygous p53 R282W mutant human embryonic stem cell line generated using TALEN-mediated precise gene editing

Stem Cell Res. 2018 Mar:27:131-135. doi: 10.1016/j.scr.2018.01.035. Epub 2018 Jan 28.

Authors

Ruoji Zhou¹, An Xu², Donghui Wang³, Dandan Zhu², Helen Mata⁴, Zijun Huo⁵, Jian Tu⁶, Mo Liu², Alaa M T Mohamed², Brittany E Jewell¹, Julian Gingold⁷, Weiya Xia⁸, Pulivarthi H Rao⁴, Mien-Chie Hung⁹, Ruiying Zhao¹⁰, Dung-Fang Lee¹¹

Affiliations

¹ 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.
² Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
³ 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, P. R. China.
⁴ Department of Pediatrics, Baylor College of Medicine, Texas Children's Cancer and Hematology Centers, Houston, TX 77030, USA.
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 Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, P. R. China.
⁶ 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, P. R. China.
⁷ Women's Health Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
⁸ Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
⁹ Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; Graduate Institute of Biomedical Sciences, Center for Molecular Medicine, China Medical University, Taichung 404, Taiwan.
¹⁰ 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.
¹¹ 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; Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Center for Precision Health, School of Biomedical Informatics and School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Electronic address: dung-fang.lee@uth.tmc.edu.

PMID: 29414603
DOI: 10.1016/j.scr.2018.01.035

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Gene Editing / methods*
Homozygote
Human Embryonic Stem Cells / metabolism*
Humans
Male
Mutation / genetics
Transcription Activator-Like Effector Nucleases / genetics
Transcription Activator-Like Effector Nucleases / metabolism*
Tumor Suppressor Protein p53 / genetics*

Substances

Tumor Suppressor Protein p53
Transcription Activator-Like Effector Nucleases

Abstract

Publication types

MeSH terms

Substances

Grants and funding