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Inhibition of Cell Division and DNA Replication Impair Mouse-Naïve Pluripotency Exit

Ariel Waisman1, Camila Vazquez Echegaray1, Claudia Solari1

  • 1Universidad de Buenos Aires, Laboratorio de Regulación Génica en Células Madre, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina; CONICET-Universidad de Buenos Aires, Instituto de Química Biológica (IQUIBICEN), Buenos Aires, Argentina.

Journal of Molecular Biology
|July 8, 2017
PubMed

Insights

Mouse embryonic stem cell differentiation requires DNA replication. This process, occurring before the S phase in G1, is crucial for initiating changes in cell identity and lineage priming.

Area of Science:

  • Stem cell biology
  • Cell cycle regulation
  • Developmental biology

Background:

  • The cell cycle influences cell fate decisions, but its role in stem cell differentiation, particularly DNA replication and mitosis, remains understudied.
  • Understanding these cell cycle phases as potential "windows of opportunity" for cell identity changes is critical.

Purpose of the Study:

  • To investigate the role of DNA replication and mitosis in mouse embryonic stem cell differentiation.
  • To determine if cell cycle progression acts as a critical window for initiating changes in cell identity during pluripotency exit.

Main Methods:

  • Established synchronized cultures of mouse embryonic stem cells exiting pluripotency.
  • Analyzed transcriptional changes during cell cycle progression.
  • Impaired DNA replication to assess its impact on differentiation, including in the absence of p53 activity.

Main Results:

  • Initial transcriptional changes during pluripotency exit do not require mitosis.
  • Conversion to primed pluripotency and lineage priming are linked to the G1 phase.
  • Impaired DNA replication significantly blocked the transcriptional switch to primed pluripotency, independent of p53-mediated DNA damage response.

Conclusions:

  • DNA replication plays a critical role in mouse embryonic stem cell differentiation.
  • Pluripotent cells appear most receptive to differentiation signals during the G1 phase, prior to DNA replication (S phase).
Keywords:
DNA replicationcell divisionmouse embryonic stem cells introductionprimitive ectoderm-like cells

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