Induction of site-specific chromosomal translocations in embryonic stem cells by CRISPR/Cas9

被引：36

作者：

Jiang, Junfeng ^{[1
,2
]}

Zhang, Li ^{[2
,3
]}

Zhou, Xingliang ^{[2
]}

Chen, Xi ^{[2
]}

Huang, Guanyi ^{[2
]}

Li, Fengsheng ^{[2
]}

Wang, Ruizhe ^{[2
]}

Wu, Nancy ^{[2
]}

Yan, Youzhen ^{[2
]}

Tong, Chang ^{[2
]}

Srivastava, Sankalp ^{[2
]}

Wang, Yue ^{[1
]}

Liu, Houqi ^{[1
,3
]}

Ying, Qi-Long ^{[2
]}

机构：

[1] Second Mil Med Univ, Dept Histol & Embryol, Res Ctr Dev Biol, Shanghai 200433, Peoples R China

[2] Univ So Calif, Keck Sch Med, Dept Stem Cell Biol & Regenerat Med, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90033 USA

[3] Second Mil Med Univ, Translat Med Ctr, Shanghai 200433, Peoples R China

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

基金：

中国国家自然科学基金;

关键词：

CHROMATIN INTERACTOME; HIGH-RESOLUTION; GENOME; REARRANGEMENTS; ENDONUCLEASE; CRISPR-CAS9; CAS9; CDX2;

D O I：

10.1038/srep21918

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Chromosomal translocation is the most common form of chromosomal abnormality and is often associated with congenital genetic disorders, infertility, and cancers. The lack of cellular and animal models for chromosomal translocations, however, has hampered our ability to understand the underlying disease mechanisms and to develop new therapies. Here, we show that site-specific chromosomal translocations can be generated in mouse embryonic stem cells (mESCs) via CRISPR/Cas9. Mouse ESCs carrying translocated chromosomes can be isolated and expanded to establish stable cell lines. Furthermore, chimeric mice can be generated by injecting these mESCs into host blastocysts. The establishment of ESC-based cellular and animal models of chromosomal translocation by CRISPR/Cas9 provides a powerful platform for understanding the effect of chromosomal translocation and for the development of new therapeutic strategies.

引用

页数：9

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