Generation and characterization of stable pig pregastrulation epiblast stem cell lines
2021
发表期刊CELL RESEARCH
ISSN1001-0602
EISSN1748-7838
DOI10.1038/s41422-021-00592-9
摘要Pig epiblast-derived pluripotent stem cells are considered to have great potential and broad prospects for human therapeutic model development and livestock breeding. Despite ongoing attempts since the 1990s, no stably defined pig epiblast-derived stem cell line has been established. Here, guided by insights from a large-scale single-cell transcriptome analysis of pig embryos from embryonic day (E) 0 to E14, specifically, the tracing of pluripotency changes during epiblast development, we developed an in vitro culture medium for establishing and maintaining stable pluripotent stem cell lines from pig E10 pregastrulation epiblasts (pgEpiSCs). Enabled by chemical inhibition of WNT-related signaling in combination with growth factors in the FGF/ERK, JAK/STAT3, and Activin/Nodal pathways, pgEpiSCs maintain their pluripotency transcriptome features, similar to those of E10 epiblast cells, and normal karyotypes after more than 240 passages and have the potential to differentiate into three germ layers. Strikingly, ultradeep in situ Hi-C analysis revealed functional impacts of chromatin 3D-spatial associations on the transcriptional regulation of pluripotency marker genes in pgEpiSCs. In practice, we confirmed that pgEpiSCs readily tolerate at least three rounds of successive gene editing and generated cloned gene-edited live piglets. Our findings deliver on the long-anticipated promise of pig pluripotent stem cells and open new avenues for biological research, animal husbandry, and regenerative biomedicine.
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收录类别SCIE
语种英语
WOS研究方向Cell Biology
WOS类目Cell Biology
WOS记录号WOS:000724064200002
出版者SPRINGERNATURE
原始文献类型Article; Early Access
引用统计
文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/134160
专题生命科学与技术学院_PI研究组_黄行许组
通讯作者Liu, Zhonghua; Zheng, Caihong; Li, Mingzhou; Han, Jianyong
作者单位
1.China Agr Univ, Coll Biol Sci, State Key Lab Agrobiotechnol, Beijing, Peoples R China;
2.Sichuan Agr Univ, Coll Anim Sci & Technol, Inst Anim Genet & Breeding, Chengdu, Sichuan, Peoples R China;
3.Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, Beijing, Peoples R China;
4.Chinese Acad Sci, Inst Stem Cell & Regenerat Med, Beijing, Peoples R China;
5.Beijing Inst Stem Cell & Regenerat Med, Beijing, Peoples R China;
6.China Agr Univ, Coll Anim Sci & Technol, Key Lab Anim Genet, Beijing, Peoples R China;
7.Yunnan Agr Univ, State Key Lab Conservat & Utilizat Bioresources Y, Kunming, Yunnan, Peoples R China;
8.Beijing Univ Agr, Anim Sci & Technol Coll, Beijing, Peoples R China;
9.Northeast Agr Univ, Coll Life Sci, Key Lab Anim Cellular & Genet Engn Heilongjiang P, Harbin, Peoples R China;
10.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China;
11.Jilin Univ, Coll Anim Sci, Jilin Prov Key Lab Anim Embryo Engn, Changchun, Jilin, Peoples R China;
12.Huazhong Agr Univ, Coll Anim Sci & Vet Med, Inst Stem Cell & Regenerat Biol, Wuhan, Hubei, Peoples R China;
13.Tsinghua Univ, Ctr Stem Cell Biol & Regenerat Med, THU PKU Ctr Life Sci, Sch Life Sci, Beijing, Peoples R China;
14.Chinese Acad Sci, Beijing Inst Genom, Key Lab Genom & Precis Med, Beijing, Peoples R China;
15.China Natl Ctr Bioinformat, Beijing, Peoples R China
推荐引用方式
GB/T 7714
Zhi, Minglei,Zhang, Jinying,Tang, Qianzi,et al. Generation and characterization of stable pig pregastrulation epiblast stem cell lines[J]. CELL RESEARCH,2021.
APA Zhi, Minglei.,Zhang, Jinying.,Tang, Qianzi.,Yu, Dawei.,Gao, Shuai.,...&Han, Jianyong.(2021).Generation and characterization of stable pig pregastrulation epiblast stem cell lines.CELL RESEARCH.
MLA Zhi, Minglei,et al."Generation and characterization of stable pig pregastrulation epiblast stem cell lines".CELL RESEARCH (2021).
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