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Androgenetic haploid embryonic stem cells produce live transgenic mice
Wei Li,Ling Shuai,Haifeng Wan,Mingzhu Dong,Meng Wang,Lisi Sang,Chunjing Feng,Guan-Zheng Luo,Tianda Li,Xin Li,Libin Wang,Qin-Yuan Zheng,Chao Sheng,Hua-Jun Wu,Zhonghua Liu,Lei Liu,Liu Wang,Xiu-Jie Wang,Xiao-Yang Zhao & Qi Zhou
Nature
Abstract
Haploids and double haploids are important resources for studying recessive traits and have large impacts on crop breeding1, but natural haploids are rare in animals. Mammalian haploids are restricted to germline cells and are occasionally found in tumours with massive chromosome loss2, 3. Recent success in establishing haploid embryonic stem (ES) cells in medaka fish4 and mice5, 6 raised the possibility of using engineered mammalian haploid cells in genetic studies. However, the availability and functional characterization of mammalian haploid ES cells are still limited. Here we show that mouse androgenetic haploid ES (ahES) cell lines can be established by transferring sperm into an enucleated oocyte. The ahES cells maintain haploidy and stable growth over 30 passages, express pluripotent markers, possess the ability to differentiate into all three germ layers in vitro and in vivo, and contribute to germlines of chimaeras when injected into blastocysts. Although epigenetically distinct from sperm cells, the ahES cells can produce viable and fertile progenies after intracytoplasmic injection into mature oocytes. The oocyte-injection procedure can also produce viable transgenic mice from genetically engineered ahES cells. Our findings show the developmental pluripotency of androgenentic haploids and provide a new tool to quickly produce genetic models for recessive traits. They may also shed new light on assisted reproduction.
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DOI:10.1038/nature11435 |
论文题目: |
Androgenetic haploid embryonic stem cells produce live transgenic mice |
英文论文题目: |
Androgenetic haploid embryonic stem cells produce live transgenic mice |
第一作者: |
Wei Li,Ling Shuai,Haifeng Wan,Mingzhu Dong,Meng Wang,Lisi Sang,Chunjing Feng,Guan-Zheng Luo,Tianda Li,Xin Li,Libin Wang,Qin-Yuan Zheng,Chao Sheng,Hua-Jun Wu,Zhonghua Liu,Lei Liu,Liu Wang,Xiu-Jie Wang,Xiao-Yang Zhao & Qi Zhou |
英文第一作者: |
Wei Li,Ling Shuai,Haifeng Wan,Mingzhu Dong,Meng Wang,Lisi Sang,Chunjing Feng,Guan-Zheng Luo,Tianda Li,Xin Li,Libin Wang,Qin-Yuan Zheng,Chao Sheng,Hua-Jun Wu,Zhonghua Liu,Lei Liu,Liu Wang,Xiu-Jie Wang,Xiao-Yang Zhao & Qi Zhou |
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2012-10-09 |
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Haploids and double haploids are important resources for studying recessive traits and have large impacts on crop breeding1, but natural haploids are rare in animals. Mammalian haploids are restricted to germline cells and are occasionally found in tumours with massive chromosome loss2, 3. Recent success in establishing haploid embryonic stem (ES) cells in medaka fish4 and mice5, 6 raised the possibility of using engineered mammalian haploid cells in genetic studies. However, the availability and functional characterization of mammalian haploid ES cells are still limited. Here we show that mouse androgenetic haploid ES (ahES) cell lines can be established by transferring sperm into an enucleated oocyte. The ahES cells maintain haploidy and stable growth over 30 passages, express pluripotent markers, possess the ability to differentiate into all three germ layers in vitro and in vivo, and contribute to germlines of chimaeras when injected into blastocysts. Although epigenetically distinct from sperm cells, the ahES cells can produce viable and fertile progenies after intracytoplasmic injection into mature oocytes. The oocyte-injection procedure can also produce viable transgenic mice from genetically engineered ahES cells. Our findings show the developmental pluripotency of androgenentic haploids and provide a new tool to quickly produce genetic models for recessive traits. They may also shed new light on assisted reproduction. |
英文摘要: |
Haploids and double haploids are important resources for studying recessive traits and have large impacts on crop breeding1, but natural haploids are rare in animals. Mammalian haploids are restricted to germline cells and are occasionally found in tumours with massive chromosome loss2, 3. Recent success in establishing haploid embryonic stem (ES) cells in medaka fish4 and mice5, 6 raised the possibility of using engineered mammalian haploid cells in genetic studies. However, the availability and functional characterization of mammalian haploid ES cells are still limited. Here we show that mouse androgenetic haploid ES (ahES) cell lines can be established by transferring sperm into an enucleated oocyte. The ahES cells maintain haploidy and stable growth over 30 passages, express pluripotent markers, possess the ability to differentiate into all three germ layers in vitro and in vivo, and contribute to germlines of chimaeras when injected into blastocysts. Although epigenetically distinct from sperm cells, the ahES cells can produce viable and fertile progenies after intracytoplasmic injection into mature oocytes. The oocyte-injection procedure can also produce viable transgenic mice from genetically engineered ahES cells. Our findings show the developmental pluripotency of androgenentic haploids and provide a new tool to quickly produce genetic models for recessive traits. They may also shed new light on assisted reproduction. |
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Nature |
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Nature |
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Wei Li,Ling Shuai,Haifeng Wan,Mingzhu Dong,Meng Wang,Lisi Sang,Chunjing Feng,Guan-Zheng Luo,Tianda Li,Xin Li,Libin Wang,Qin-Yuan Zheng,Chao Sheng,Hua-Jun Wu,Zhonghua Liu,Lei Liu,Liu Wang,Xiu-Jie Wang,Xiao-Yang Zhao & Qi Zhou. Androgenetic haploid embryonic stem cells produce live transgenic mice. Nature DOI:10.1038/nature11435 |
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