Germ cell specification and pluripotency in mammals: a perspective from early embryogenesis

Abstract

Germ cells are unique cell types that generate a totipotent zygote upon fertilization, giving rise to the next generation in mammals and many other multicellular organisms. How germ cells acquire this ability has been of considerable interest. In mammals, primordial germ cells (PGCs), the precursors of sperm and oocytes, are specified around the time of gastrulation. PGCs are induced by signals from the surrounding extra-embryonic tissues to the equipotent epiblast cells that give rise to all cell types. Currently, the mechanism of PGC specification in mammals is best understood from studies in mice. Following implantation, the epiblast cells develop as an egg cylinder while the extra-embryonic ectoderm cells which are the source of important signals for PGC specification are located over the egg cylinder. However, in most cases, including humans, the epiblast cells develop as a planar disc, which alters the organization and the source of the signaling for cell fates. This, in turn, might have an effect on the precise mechanism of PGC specification in vivo as well as in vitro using pluripotent embryonic stem cells. Here, we discuss how the key early embryonic differences between rodents and other mammals may affect the establishment of the pluripotency network in vivo and in vitro, and consequently the basis for PGC specification, particularly from pluripotent embryonic stem cells in vitro.

The Formation and Migration of Primordial Germ Cells in Mouse and Man

“…Moreover, analyses of single-cell gene expression in selected embryonic populations have identified key regulators and global transcription events associated with mouse PGC specification (reviewed in Hayashi et al 2007;Irie et al 2015a).…”

Signals and transcription factors for specification of human germ cells

“…Our knowledge on germ cell specification is primarily based on observations in the murine system, in which the germ cell fate is initiated in the proximal epiblast around embryonic day 6.5 (E6.5) (1,2). At E7.75 mouse PGCs start migrating along the developing hindgut to the genital ridges, where they arrive at E10.5 (1).…”

Discrimination of Stem Cell Status after Subjecting Cynomolgus Monkey Pluripotent Stem Cells to Naïve Conversion

“…Primed PSCs from several animal species have been attempted to convert into a naïve state111213. Properties of a naïve state are a domed-shape colony morphology, leukaemia inhibitory factor (LIF) dependency, ability to use mitochondrial respiration, pluripotent transcriptomal circuitry, transcriptional status resembling pre-implantation epiblasts, and efficient ability to contribute to chimeric embryos with subsequent germline transmission.…”