Embryonic Stem Cells License a High Level of Dormant Origins to Protect the Genome against Replication Stress

Xin Quan Ge, Jinah Han, Ee Chun Cheng, Satoru Yamaguchi, Naoko Shima, Jean Leon Thomas, Haifan Lin

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)185-194
Number of pages10
JournalStem Cell Reports
Issue number2
StatePublished - 2015

Bibliographical note

Funding Information:
We thank Felix Rivera-Molina for assistance with SIM. This work was funded by a grant from the Connecticut Stem Cell Research Fund (10SCA05) to X.Q.G. and the G. Harold and Leica Y. Mathers Award to H.L.

Publisher Copyright:
© 2015 The Authors.


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