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Delayed DNA replication in haploid human embryonic stem cells.

Matthew M Edwards1, Michael V Zuccaro2,3, Ido Sagi4

  • 1Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.

Genome Research
|November 23, 2021
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Summary
This summary is machine-generated.

Haploid stem cells often become diploid due to abnormal DNA replication. This study reveals delayed replication in specific autosomal regions, potentially explaining this process in human embryonic stem cells (ESCs).

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Area of Science:

  • Cell Biology
  • Genetics
  • Developmental Biology

Background:

  • Haploid human embryonic stem cells (ESCs) are valuable for genetic studies but prone to diploidization.
  • The mechanisms driving this rapid diploidization remain incompletely understood.

Purpose of the Study:

  • To investigate the role of aberrant DNA replication in the diploidization of haploid ESCs.
  • To compare DNA replication timing between haploid and diploid ESCs.

Main Methods:

  • Profiling DNA replication timing in isogenic haploid and diploid human ESCs.
  • Analyzing differences in replication timing, particularly focusing on chromosomal regions.

Main Results:

  • Haploid ESCs exhibit earlier X Chromosome replication, consistent with absent X-Chromosome inactivation.
  • Twenty-one autosomal regions showed delayed replication in haploid ESCs, extending into G2/M phase.
  • These delayed regions are quiescent and also underreplicated in placental cells, suggesting a link to X-Chromosome dosage.

Conclusions:

  • Aberrant DNA replication, specifically delayed autosomal replication in haploid ESCs, contributes to diploidization.
  • Increased X-Chromosome dosage may induce delayed autosomal replication.
  • Incomplete replication may trigger cell cycle re-entry and whole genome duplication, leading to diploidization.