Enhancing the precision of genetic lineage tracing using dual recombinases

被引：200

作者：

He, Lingjuan ^{[1
,2
]}

Li, Yan ^{[1
,2
]}

Li, Yi ^{[1
,2
]}

Pu, Wenjuan ^{[1
,2
]}

Huang, Xiuzhen ^{[1
,2
]}

Tian, Xueying ^{[1
,2
]}

Wang, Yue ^{[1
,2
]}

Zhang, Hui ^{[1
,2
]}

Liu, Qiaozhen ^{[1
,2
]}

Zhang, Libo ^{[1
,2
]}

Zhao, Huan ^{[1
,2
]}

Tang, Juan ^{[1
,2
]}

Ji, Hongbin ^{[1
,3
]}

Cai, Dongqing ^{[4
]}

Han, Zhibo ^{[5
,6
,7
]}

Han, Zhongchao ^{[5
,6
,7
]}

Nie, Yu ^{[7
,8
]}

Hu, Shengshou ^{[7
,8
]}

Wang, Qing-Dong ^{[9
]}

Sun, Ruilin ^{[10
]}

Fei, Jian ^{[10
]}

Wang, Fengchao ^{[11
]}

Chen, Ting ^{[11
]}

Yan, Yan ^{[12
]}

Huang, Hefeng ^{[13
]}

Pu, William T. ^{[14
,15
]}

Zhou, Bin ^{[1
,4
,16
]}

机构：

[1] Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Cell Biol,CAS Ctr Excellence Mol C, Shanghai, Peoples R China

[2] Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutrit Sci, Shanghai, Peoples R China

[3] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China

[4] Jinan Univ, Inst Aging & Regenerat Med, Minist Educ, Key Lab Regenerat Med, Guangzhou, Guangdong, Peoples R China

[5] Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin, Peoples R China

[6] Chinese Acad Med Sci, Hosp Blood Dis, Tianjin, Peoples R China

[7] Peking Union Med Coll, Tianjin, Peoples R China

[8] Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing, Peoples R China

[9] AstraZeneca, IMED Biotech Unit, Cardiovasc & Metab Dis, Biosci Heart Failure, Gothenburg, Sweden

[10] Shanghai Model Organisms Ctr Inc, Shanghai, Peoples R China

[11] Natl Inst Biol Sci, Beijing, Peoples R China

[12] Fudan Univ, Zhongshan Hosp, Shanghai, Peoples R China

[13] Shanghai Jiao Tong Univ, Sch Med, Int Peace Matern & Child Hlth Hosp, Shanghai, Peoples R China

[14] Boston Childrens Hosp, Dept Cardiol, Boston, MA USA

[15] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA

[16] Tianjin Med Univ, Collaborat Innovat Ctr Tianjin Med Epigenet, Tianjin, Peoples R China

来源：

NATURE MEDICINE | 2017年 / 23卷 / 12期

基金：

中国博士后科学基金; 美国国家科学基金会;

关键词：

CARDIAC STEM-CELLS; CRE RECOMBINASE; C-KIT(+) CELLS; PERIPORTAL HEPATOCYTES; ENDOTHELIAL-CELLS; DNA RECOMBINATION; MAMMALIAN-CELLS; DRE RECOMBINASE; NEURAL CREST; ADULT;

D O I：

10.1038/nm.4437

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The Cre-loxP recombination system is the most widely used technology for in vivo tracing of stem or progenitor cell lineages. The precision of this genetic system largely depends on the specificity of Cre recombinase expression in targeted stem or progenitor cells. However, Cre expression in nontargeted cell types can complicate the interpretation of lineage-tracing studies and has caused controversy in many previous studies. Here we describe a new genetic lineage tracing system that incorporates the Dre-rox recombination system to enhance the precision of conventional Cre-loxP-mediated lineage tracing. The Dre-rox system permits rigorous control of Cre-loxP recombination in lineage tracing, effectively circumventing potential uncertainty of the cell-type specificity of Cre expression. Using this new system we investigated two topics of recent debates-the contribution of c-Kit(+) cardiac stem cells to cardiomyocytes in the heart and the contribution of Sox9(+) hepatic progenitor cells to hepatocytes in the liver. By overcoming the technical hurdle of nonspecific Cre-loxP-mediated recombination, this new technology provides more precise analysis of cell lineage and fate decisions and facilitates the in vivo study of stem and progenitor cell plasticity in disease and regeneration.

引用

页码：1488 / +

页数：13

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