In Vitro Derivation and Propagation of Spermatogonial Stem Cell Activity from Mouse Pluripotent Stem Cells

Cell Rep. 2016 Dec 6;17(10):2789-2804. doi: 10.1016/j.celrep.2016.11.026.


The in vitro derivation and propagation of spermatogonial stem cells (SSCs) from pluripotent stem cells (PSCs) is a key goal in reproductive science. We show here that when aggregated with embryonic testicular somatic cells (reconstituted testes), primordial germ cell-like cells (PGCLCs) induced from mouse embryonic stem cells differentiate into spermatogonia-like cells in vitro and are expandable as cells that resemble germline stem cells (GSCs), a primary cell line with SSC activity. Remarkably, GSC-like cells (GSCLCs), but not PGCLCs, colonize adult testes and, albeit less effectively than GSCs, contribute to spermatogenesis and fertile offspring. Whole-genome analyses reveal that GSCLCs exhibit aberrant methylation at vulnerable regulatory elements, including those critical for spermatogenesis, which may restrain their spermatogenic potential. Our study establishes a strategy for the in vitro derivation of SSC activity from PSCs, which, we propose, relies on faithful epigenomic regulation.

Keywords: DNA methylation; embryonic stem cells; epigenetic reprogramming; primordial germ cells; spermatogonial stem cells; testes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Germline Stem Cells / cytology*
  • Animals
  • Cell Proliferation / genetics
  • Male
  • Mice
  • Pluripotent Stem Cells / cytology*
  • Spermatogenesis / genetics*
  • Spermatogonia / cytology
  • Testis / cytology*