RT Journal
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
T1 Delayed DNA replication in haploid human embryonic stem cells
JF Genome Research 
JO Genome Research 
YR 2021 
FD December 01 
VO 31 
IS 12 
SP 2155 
OP 2169 
DO 10.1101/gr.275953.121 
UL http://genome.cshlp.org/content/31/12/2155.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. 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.