modeling-osteosarcoma-using-li-fraumeni-syndrome-patient-derived

Modeling Osteosarcoma Using Li-Fraumeni Syndrome Patient-derived Induced Pluripotent Stem Cells

Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer disorder. Patients with LFS are predisposed to a various type of tumors, including ...

The University of Texas Health Science Center at Houston

the first affiliated hospital of Sun Yat-sen University

The Histogenesis of Ewing Sarcoma.

The Retinoblastoma 1 (RB1) tumor suppressor, a member of the Retinoblastoma gene family, functions as a pocket protein for the functional binding of E2F transcription factors. About 1/3 of retinoblastoma patients harbor a germline RB1 mutation or deletion, leading to the development of retinoblastoma. Here, we demonstrate generation of a heterozygous deletion of the RB1 gene in the H1 human embryonic stem cell line using CRISPR/Cas9 nickase genome editing. The RB1 heterozygous knockout H1 cell line shows a normal karyotype, maintains a pluripotent state, and is capable of differentiation to the three germline layers.

Generation of human embryonic stem cell line with heterozygous RB1 deletion by CRIPSR/Cas9 nickase.

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.

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

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.

Article	Year
The Histogenesis of Ewing Sarcoma. Cancer reports and reviews\| PubMed ID: 28626837	2017
Generation of human embryonic stem cell line with heterozygous RB1 deletion by CRIPSR/Cas9 nickase. Stem cell research\| PubMed ID: 29414415	2018
A homozygous p53 R282W mutant human embryonic stem cell line generated using TALEN-mediated precise gene editing. Stem cell research\| PubMed ID: 29414603	2018
Establishment of a human embryonic stem cell line with homozygous TP53 R248W mutant by TALEN mediated gene editing. Stem cell research\| PubMed ID: 29730572	2018

Jian Tu

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