The miR-290-295 cluster promotes pluripotency maintenance by regulating cell cycle phase distribution in mouse embryonic stem cells

Zsuzsanna Lichner, Emodouble Acuteke Páll, Andrea Kerekes, Éva Pállinger, Pouneh Maraghechi, Zsuzsanna Bodouble acutesze, Elen Gócza

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

The mmu-miR-290-295 cluster codes for a family of microRNAs (miRNAs) that are expressed de novo during early embryogenesis and are specific for mouse embryonic stem cells (ESC) and embryonic carcinoma cells (ECC). Detailed sequence analysis and alignment studies of miR-290-295 precursors demonstrated that the cluster has evolved by repeated duplication events of the ancient miR-290 precursor. We show that under serum starvation, overexpression of miR-290-295 miRNAs withhold ES cells from early differentiation, ensures their high proliferation rate and capacity for forming alkaline phosphate positive colonies. Transcriptome analysis revealed that differentiation related marker genes are underexpressed upon high miR-290-295 level. Importantly, miR-290-295 overexpression prevents ES cells from accumulation in G1 phase at low serum level, and seems to regulate cell cycle in different phases. Our data underline that miR-290-295 miRNAs contribute to the natural absence of G1 checkpoint in embryonic stem cells. We define the cell cycle regulators Wee1 and Fbxl5 as potential direct targets of miR-290-295 miRNAs in vitro. Our results suggest that miR-290-295 miRNAs exhibit their effect predominantly through the regulation of cell cycle phase distribution.

Original languageEnglish
Pages (from-to)11-24
Number of pages14
JournalDifferentiation
Volume81
Issue number1
DOIs
Publication statusPublished - Jan 1 2011

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Keywords

  • Differentiation
  • Embryonic stem cells
  • Fbxl5
  • MiR-290-295 cluster
  • MicroRNAs
  • Wee1

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology
  • Cancer Research

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