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

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2015 Jul 21

PMID 26190528

Citations 28

Authors

Xin Quan Ge

Jinah Han

Ee-Chun Cheng

Satoru Yamaguchi

Naoko Shima

Jean-Leon Thomas

Haifan Lin

Affiliations

Soon will be listed here.

Abstract

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.

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