学術雑誌論文 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, Hiroyuki  ,  Saitou, Mitinori

17 ( 10 )  , pp.2789 - 2804 , 2016-12-06 , Elsevier B.V.
ISSN:2211-1247
内容記述
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.
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http://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/217467/1/j.celrep.2016.11.026.pdf

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