Prdm14 promotes germline fate and naive pluripotency by repressing FGF signalling and DNA methylation.

Nils Grabole,Shinseog Kim,Erna Magnúsdóttir,Jamie A Hackett,Harry G Leitch,Fuchou Tang,M Azim Surani,Julia Tischler

doi:10.1038/embor.2013.67

Nils Grabole, Shinseog Kim + Show 6 more

Open Access

https://doi.org/10.1038/embor.2013.67

Copy DOI

Journal: EMBO Reports	Publication Date: May 14, 2013
Citations: 165	License type: CC BY 3.0

Affiliation: Wellcome/Cancer Research UK Gurdon Institute

Abstract

Primordial germ cells (PGCs) and somatic cells originate from postimplantation epiblast cells in mice. As pluripotency is lost upon differentiation of somatic lineages, a naive epigenome and the pluripotency network are re-established during PGC development. Here we demonstrate that Prdm14 contributes not only to PGC specification, but also to naive pluripotency in embryonic stem (ES) cells by repressing the DNA methylation machinery and fibroblast growth factor (FGF) signalling. This indicates a critical role for Prdm14 in programming PGCs and promoting pluripotency in ES cells.

Highlights

Primordial germ cell (PGC) specification in mice commences in the proximal epiblast cells in response to BMP4 signalling at embryonic day (E) 6.25 just before the onset of gastrulation
As initiation of lineage priming and perturbation of the pluripotency network are evoked by fibroblast growth factor (FGF) signalling in ES cells [10], we examined the status of this pathway in PGCs
Our analysis suggests that Prdm14 is involved in the downregulation of Fgfr2 and repression of extracellular signal-regulated kinase (ERK) activation, as well as the repression of DNA methylation, which together may ensure repression of the somatic programme in PGCs and re-expression of genes of the germ cell lineage

Summary

Introduction

Primordial germ cell (PGC) specification in mice commences in the proximal epiblast cells in response to BMP4 signalling at embryonic day (E) 6.25 just before the onset of gastrulation. By E7.25, approximately 30–40 founder PGCs are established following expression of the three key regulators: Prdm (BLIMP1), Prdm and Tcfap2c (AP2g) [1,2,3]. The segregation of PGCs from neighbouring mesoderm progenitor cells entails repression and reversal of the initiation of the somatic programme, and re-establishment of the pluripotency network in conjunction with changes in chromatin modifications [4,5]. Expression of Prdm is confined to PGCs and pluripotent cells only, where it has a critical role for the regulation of pluripotency genes, and it promotes resetting of the epigenome [3,6]. Prdm14deficient PGCs are specified, but fail to proliferate and are eventually lost during migration towards the genital ridges.

Methods

Results

Conclusion