Embryonic Stem Cells License a High Level of Dormant Origins to Protect the Genome against Replication Stress
2015-08-11
发表期刊STEM CELL REPORTS (IF:5.9[JCR-2023],5.9[5-Year])
ISSN2213-6711
卷号5期号:2页码:185-194
发表状态已发表
DOI10.1016/j.stemcr.2015.06.002
摘要Maintaining genomic integrity during DNA replication is essential for stem cells. DNA replication origins are licensed by the MCM2-7 complexes, with most of them remaining dormant. Dormant origins (DOs) rescue replication fork stalling in S phase and ensure genome integrity. However, it is not known whether DOs exist and play important roles in any stem cell type. Here, we show that embryonic stem cells (ESCs) contain more DOs than tissue stem/progenitor cells such as neural stem/progenitor cells (NSPCs). Partial depletion of DOs does not affect ESC self-renewal but impairs their differentiation, including toward the neural lineage. However, reduction of DOs in NSPCs impairs their self-renewal due to accumulation of DNA damage and apoptosis. Furthermore, mice with reduced DOs show abnormal neurogenesis and semi-embryonic lethality. Our results reveal that ESCs are equipped with more DOs to better protect against replicative stress than tissue-specific stem/progenitor cells.
收录类别SCI
语种英语
资助项目Connecticut Stem Cell Research Fund[10SCA05]
WOS研究方向Cell Biology
WOS类目Cell & Tissue Engineering ; Cell Biology
WOS记录号WOS:000359428800004
出版者CELL PRESS
WOS关键词MEIER-GORLIN SYNDROME ; DNA-REPLICATION ; COMPLEX ; DEFICIENCY ; MICE ; FAILURE ; MCM2-7 ; SITE ; HBO1 ; CDT1
原始文献类型Article
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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/2155
专题免疫化学研究所
生命科学与技术学院
免疫化学研究所_特聘教授组_干细胞生物学实验室
通讯作者Lin, Haifan
作者单位
1.Yale Univ, Sch Med, Yale Stem Cell Ctr, New Haven, CT 06520 USA
2.Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06520 USA
3.Yale Univ, Sch Med, Yale Cardiovasc Res Ctr, New Haven, CT 06520 USA
4.Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA
5.ShanghaiTech Univ, SIAIS, Shanghai 201210, Peoples R China
6.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
7.Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA
通讯作者单位上海科技大学;  生命科学与技术学院
推荐引用方式
GB/T 7714
Ge, Xin Quan,Han, Jinah,Cheng, Ee-Chun,et al. Embryonic Stem Cells License a High Level of Dormant Origins to Protect the Genome against Replication Stress[J]. STEM CELL REPORTS,2015,5(2):185-194.
APA Ge, Xin Quan.,Han, Jinah.,Cheng, Ee-Chun.,Yamaguchi, Satoru.,Shima, Naoko.,...&Lin, Haifan.(2015).Embryonic Stem Cells License a High Level of Dormant Origins to Protect the Genome against Replication Stress.STEM CELL REPORTS,5(2),185-194.
MLA Ge, Xin Quan,et al."Embryonic Stem Cells License a High Level of Dormant Origins to Protect the Genome against Replication Stress".STEM CELL REPORTS 5.2(2015):185-194.
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