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

Yukiko Ishikura, Yukihiro Yabuta, Hiroshi Ohta, Katsuhiko Hayashi, Tomonori Nakamura, Ikuhiro Okamoto, Takuya Yamamoto, Kazuki Kurimoto, Kenjiro Shirane, Hiroyuki Sasaki, Mitinori Saitou

研究成果: Contribution to journalArticle査読

70 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)2789-2804
ページ数16
ジャーナルCell Reports
17
10
DOI
出版ステータス出版済み - 12 6 2016

All Science Journal Classification (ASJC) codes

  • 生化学、遺伝学、分子生物学(全般)

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