Primordial Germ Cells in Mice

Abstract

SUMMARYGerm cell development creates totipotency through genetic as well as epigenetic regulation of the genome function. Primordial germ cells (PGCs) are the first germ cell population established during development and are immediate precursors for both the oocytes and spermatogonia. We here summarize recent findings regarding the mechanism of PGC development in mice. We focus on the transcriptional and signaling mechanism for PGC specification, potential pluripotency, and epigenetic reprogramming in PGCs and strategies for the reconstitution of germ cell development using pluripotent stem cells in culture. Continued studies on germ cell development may lead to the generation of totipotency in vitro, which should have a profound influence on biological science as well as on medicine.

Mechanism and Reconstitution In Vitro of Germ Cell Development in Mammals

“…To carry out this fundamental role, primordial germ cells (PGCs), the precursors for the spermatozoa and the oocytes, undergo a number of unique events prior to their differentiation into spermatogonial stem cells (SSCs) or oocytes, which include repression of somatic programs, (re)acquisition of potential pluripotency, and reprogramming of epigenome information, for which, in the last decade, we and other groups have clarified at least a part of the molecular mechanisms Saitou and Yamaji 2012;. Based on these studies, we have successfully reconstituted the mouse germ cell specification pathway in culture: The embryonic stem cells (ESCs)/ induced pluripotent stem cells (iPSCs) are induced into epiblast-like cells (EpiLCs), which are in turn induced into PGC-like cells (PGCLCs) with robust capacities both for spermatogenesis and oogenesis (Hayashi et al 2011(Hayashi et al , 2012.…”

The DLK1-MEG3 locus in malignant cells of proposed primordial germ cell origins.

“…General reprogramming and transformation into either male or female germ cells [39,89]. The appearance of PGCs at the allantois, a region of the extraembryonic yolk sac, at E7.5 occurs at a similar time and region as the first appearance of hemangioblasts and hematopoietic islands [90,91].…”

“…As the precursors of gametes, primordial germ cells (PGCs) first appear in the developing epiblast, then undergo extensive chromatin remodeling which erases and reestablishes genomic imprinting patterns [39,40]. Interestingly, there are significant overlaps between the transitions into and out of proliferation by PGCs and changes to their epigenome ( Figure 5A) [41].…”

“…Thus, assessing a role for this protein Interestingly, while the mechanisms by which DLK1 influence cell proliferation are still largely unknown and are often unique to a given cell type, DLK1 is a known marker of certain normal stem cells and CSC populations [10,11,34,154]. Considering that EC is regarded as the stem cell within teratocarcinomas, and that EC cells exhibit certain aspects of pluripotency, DLK1 may represent a novel biomarker for EC as a product of aberrant genomic imprinting in developing PGCs during their transition to a pluripotent stem-like state [30,39,50,69].…”

“…Among these changes lies the complete erasure and reestablishment of genomic imprinting patterns [39]. Improper maintenance of genomic imprinting is found in several types of cancers and other growth-related…”