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      Reconstitution of the mouse germ cell specification pathway in culture by pluripotent stem cells.

      Cell

      Animals, Cell Culture Techniques, Cell Differentiation, Cell Proliferation, Embryonic Stem Cells, cytology, metabolism, Gene Expression Profiling, Germ Cells, Germ Layers, Induced Pluripotent Stem Cells, Mice, Pluripotent Stem Cells, Spermatogenesis

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          Abstract

          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. Copyright © 2011 Elsevier Inc. All rights reserved.

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          Journal
          21820164
          10.1016/j.cell.2011.06.052

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