Nuclear reprogramming in mouse primordial germ cells: epigenetic contribution

Abstract

The unique capability of germ cells to give rise to a new organism, allowing the transmission of primary genetic information from generation to generation, depends on their epigenetic reprogramming ability and underlying genomic totipotency. Recent studies have shown that genome-wide epigenetic modifications, referred to as "epigenetic reprogramming", occur during the development of the gamete precursors termed primordial germ cells (PGCs) in the embryo. This reprogramming is likely to be critical for the germ line development itself and necessary to erase the parental imprinting and setting the base for totipotency intrinsic to this cell lineage. The status of genome acquired during reprogramming and the associated expression of key pluripotency genes render PGCs susceptible to transform into pluripotent stem cells. This may occur in vivo under still undefined condition, and it is likely at the origin of the formation of germ cell tumors. The phenomenon appears to be reproduced under partly defined in vitro culture conditions, when PGCs are transformed into embryonic germ (EG) cells. In the present paper, I will try to summarize the contribution that epigenetic modifications give to nuclear reprogramming in mouse PGCs.

Figure 1

PGC development and associated epigenetic events in the mouse embryo. Changes in DNA methylation (DNAm) and histone modifications are represented by different shading intensity.

Figure 2

PGC transformation in EG cells. The process is schematically subdivided in to three main steps: rapid 1 day reprogramming processes involving TSA-induced epigenetic modifications and resetting of various gene and intracellular signalling pathways, a mid-time (2–4 days) establishment of a LIF/STAT3-dependent self-renewal circuit, and the formation of EG cell colonies requiring 7–10 days of culture. Various growth factors and compounds controlling each steps are reported; a cell monolayer producing KL and other not identified compounds is also represented.