Delayed DNA replication in haploid human embryonic stem cells

Matthew M. Edwards, Michael V. Zuccaro, Ido Sagi, Qiliang Ding, Dan Vershkov, Nissim Benvenisty, Dieter Egli, Amnon Koren*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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. We also identified 21 autosomal regions that had 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 underreplicated 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.

Original languageAmerican English
Pages (from-to)2155-2169
Number of pages15
JournalGenome Research
Volume31
Issue number12
DOIs
StatePublished - Dec 2021

Bibliographical note

Publisher Copyright:
© 2021 Edwards et al.

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