Heterogeneity of primordial germ cells

Abstract

Primordial germ cells (PGCs) must complete a complex and dynamic developmental program during embryogenesis to establish the germline. This process is highly conserved and involves a diverse array of tasks required of PGCs, including migration, survival, sex differentiation, and extensive epigenetic reprogramming. A common theme across many organisms is that PGC success is heterogeneous: only a portion of all PGCs complete all these steps while many other PGCs are eliminated from further germline contribution. The differences that distinguish successful PGCs as a population are not well understood. Here, we examine variation that exists in PGCs as they navigate the many stages of this developmental journey. We explore potential sources of PGC heterogeneity and their potential implications in affecting germ cell behaviors. Lastly, we discuss the potential for PGC development to function as a multistage selection process that assesses heterogeneity in PGCs to refine germline quality.

Keywords: Apoptosis; Cell individuality; Epigenetics; Germ cell; Heterogeneity; Migration; Natural selection; Primordial germ cell; Quality control; Selection; Sex differentiation.

Fig. 1

PGCs transit through multiple cell states during development but remain a single cell type defined by an uncommitted sexual identity. Cell states are not necessarily discrete nor mutually exclusive. We consider germ cells to encompass all cell types with gametogenic potential, including PGCs and sex-differentiated oogonia and prospermatogonia.

Fig. 2

Readouts of PGC Heterogeneity. Snapshots of the reproductive life cycle evidence potential readouts of heterogeneity. These readouts can be broadly surveyed across many model organisms. Key phases of potential heterogeneity occur during specification, migration, proliferation, sex determination, survival, differentiation, and gametogenesis. Specific readouts may be applicable several cell states.

Fig. 3

Determinants of PGC Heterogeneity. For the various cell types, different underlying cell states can be causes for heterogeneity, impacting cell type transition as well as impacting the fitness of progeny.