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Differentiation of a Human Neural Stem Cell Line on Three Dimensional Cultures, Analysis of MicroRNA and Putative Target Genes
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Differentiation of a Human Neural Stem Cell Line on Three Dimensional Cultures, Analysis of MicroRNA and Putative Target Genes

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MicroRNAs regulate p21(Waf1/Cip1) protein expression and the DNA damage response in human embryonic stem cells

Dasa Dolezalova1, Marek Mraz, Tomas Barta

  • 1Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Kamenice 3/A1, Brno, Czech Republic.

Stem Cells (Dayton, Ohio)
|April 19, 2012
PubMed

Insights

MicroRNAs regulate p21 protein levels in human embryonic stem cells (hESCs), impacting cell cycle control. The miR-302 family specifically suppresses p21 protein, revealing a novel mechanism in DNA damage response.

Area of Science:

  • Stem Cell Biology
  • Molecular Biology
  • Epigenetics

Background:

  • Human embryonic stem cells (hESCs) exhibit a nonfunctional p53-p21 axis in the G1/S checkpoint.
  • p21 protein is undetectable in hESCs despite detectable p21 mRNA after DNA damage response (DDR).

Purpose of the Study:

  • To investigate the role of microRNAs (miRNAs) in regulating p21 protein expression in hESCs.
  • To elucidate the mechanism controlling the G1/S checkpoint in hESCs.

Main Methods:

  • Analysis of miRNA expression profiles in hESCs.
  • Investigating the direct interaction between specific miRNAs and p21 mRNA.
  • Assessing the impact of miRNA modulation on p21 protein levels and cell cycle progression.

Main Results:

  • The microRNA pathway, particularly the hESC-enriched miR-302 family, directly regulates p21 protein expression.
  • DNA damage response in hESCs upregulates numerous miRNAs, including the miR-302 family.
  • The miR-302 family suppresses p21 protein levels, offering a novel regulatory mechanism.

Conclusions:

  • MicroRNAs play a critical role in controlling p21 protein levels in hESCs.
  • The miR-302 family's regulation of p21 is a key mechanism for cell cycle control and DNA damage response in hESCs.
  • This study reveals a novel function for miR-302s in hESCs, impacting fundamental cellular processes.

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