||In Vitro Derivation and Propagation of Spermatogonial Stem Cell Activity from Mouse Pluripotent Stem Cells
Ishikura, Yukiko ,
Yabuta, Yukihiro ,
Ohta, Hiroshi ,
Hayashi, Katsuhiko ,
Nakamura, Tomonori ,
Okamoto, Ikuhiro ,
Yamamoto, Takuya ,
Kurimoto, Kazuki ,
Shirane, Kenjiro ,
Sasaki, HiroyukiSaitou, Mitinori
2804 , 2016-12-06 , Elsevier B.V.
マウス多能性幹細胞から精子幹細胞を試験管内で誘導 : 精子形成全過程の試験管内誘導の基盤形成. 京都大学プレスリリース. 2016-12-07.
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.