Cell
Volume 146, Issue 4, 19 August 2011, Pages 519-532
Journal home page for Cell

Article
Reconstitution of the Mouse Germ Cell Specification Pathway in Culture by Pluripotent Stem Cells

https://doi.org/10.1016/j.cell.2011.06.052Get rights and content
Under an Elsevier user license
open archive

Summary

The generation of properly functioning gametes in vitro requires reconstitution of the multistepped pathway of germ cell development. We demonstrate here the generation of primordial germ cell-like cells (PGCLCs) in mice with robust capacity for spermatogenesis. PGCLCs were generated from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) through epiblast-like cells (EpiLCs), a cellular state highly similar to pregastrulating epiblasts but distinct from epiblast stem cells (EpiSCs). Reflecting epiblast development, EpiLC induction from ESCs/iPSCs is a progressive process, and EpiLCs highly competent for the PGC fate are a transient entity. The global transcription profiles, epigenetic reprogramming, and cellular dynamics during PGCLC induction from EpiLCs meticulously capture those associated with PGC specification from the epiblasts. Furthermore, we identify Integrin-β3 and SSEA1 as markers that allow the isolation of PGCLCs with spermatogenic capacity from tumorigenic undifferentiated cells. Our findings provide a paradigm for the first step of in vitro gametogenesis.

Highlights

► Generation of primordial germ cell-like cells (PGCLCs) from ESCs and iPSCs ► PGCLC induction occurs via an epiblast-like state, mimicking PGC generation in vivo ► PGCLCs contribute to spermatogenesis and produce fertile offspring ► Integrin-β3 and SSEA1 mark PGCLCs and allow purification from teratogenic cells

Cited by (0)