RT Journal Article
SR Electronic
T1 Delayed DNA replication in haploid human embryonic stem cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.05.11.443666
DO 10.1101/2021.05.11.443666
A1 Edwards, Matthew M.
A1 Zuccaro, Michael V.
A1 Sagi, Ido
A1 Ding, Qiliang
A1 Vershkov, Dan
A1 Benvenisty, Nissim
A1 Egli, Dieter
A1 Koren, Amnon
YR 2021
UL http://biorxiv.org/content/early/2021/05/12/2021.05.11.443666.abstract
AB Haploid human embryonic stem cells (ESCs) provide a powerful genetic system but diploidize at high rates. We hypothesized that diploidization results from aberrant DNA replication. To test this, we profiled DNA replication timing in isogenic haploid and diploid ESCs. The greatest difference was the earlier replication of the X chromosome in haploids, consistent with the lack of X chromosome inactivation. Surprisingly, we also identified 21 autosomal regions that had dramatically delayed replication in haploids, extending beyond the normal S phase and into G2/M. Haploid-delays comprised a unique set of quiescent genomic regions that are also under-replicated in polyploid placental cells. The same delays were observed in female ESCs with two active X chromosomes, suggesting that increased X chromosome dosage may cause delayed autosomal replication. We propose that incomplete replication at the onset of mitosis could prevent cell division and result in re-entry into the cell cycle and whole genome duplication.DNA replication timing of haploid ESCs profiled by WGSExtreme replication timing delays in haploid ESCs at unique genomic regionsReplication delays associate with X-chromosome dosage in multiple systemsReplication delayed regions correspond to underreplication in mouse polyploid cellsCompeting Interest StatementThe authors have declared no competing interest.