Sequence-specific regulator Prdm14 safeguards mouse ESCs from entering extraembryonic endoderm fates

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Structure-function Studies in Mouse Embryonic Stem Cells Using Recombinase-mediated Cassette Exchange
15:13

Structure-function Studies in Mouse Embryonic Stem Cells Using Recombinase-mediated Cassette Exchange

Published on: April 27, 2017

Ziyang Ma1, Tomek Swigut, Anton Valouev

  • 1Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California, USA.

Nature Structural & Molecular Biology
|December 25, 2010
PubMed

Insights

Prdm14 protein maintains mouse embryonic stem cell (mESC) identity by blocking differentiation into extraembryonic endoderm (ExEn). It acts as both a repressor and activator, influencing key self-renewal and differentiation genes.

Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Epigenetics

Background:

  • Prdm14 is a transcription factor expressed in pluripotent cells.
  • Its precise role in maintaining embryonic stem cell (ESC) identity is not fully understood.

Purpose of the Study:

  • To investigate the function of Prdm14 in mouse ESC (mESC) maintenance and differentiation.
  • To elucidate the molecular mechanisms by which Prdm14 regulates cell fate decisions.

Main Methods:

  • Analysis of Prdm14 expression in mESCs and early embryos.
  • Functional studies involving Prdm14 knockdown and overexpression in mESCs.
  • Chromatin immunoprecipitation sequencing (ChIP-seq) to identify Prdm14-bound genomic regions.
  • Reporter assays to assess transcriptional regulation.

Main Results:

  • Prdm14 expression is restricted to pluripotent cells.
  • Prdm14 prevents the induction of extraembryonic endoderm (ExEn) fates in mESCs.
  • Overexpression of Prdm14 inhibits ExEn differentiation.
  • Prdm14 directly represses genes involved in ExEn differentiation and activates genes promoting mESC self-renewal.
  • Prdm14 shares genomic binding sites with key pluripotency factors Nanog and Oct4.

Conclusions:

  • Prdm14 is a crucial regulator of mESC identity, acting as a molecular switch.
  • It safeguards pluripotency by actively repressing differentiation pathways and promoting self-renewal.
  • Prdm14 integrates into the core transcriptional network governing stem cell fate.

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