In Vitro Derivation and Propagation of Spermatogonial Stem Cell Activity from Mouse Pluripotent Stem Cells
In Vitro Derivation and Propagation of Spermatogonial Stem Cell Activity from Mouse Pluripotent Stem Cells
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DOI：
10.1016/j.celrep.2016.11.026
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发表时间：
2016-12-06
期刊：
影响因子：
8.8
通讯作者：
Saitou, Mitinori
中科院分区：
文献类型：
--
作者：
Ishikura, Yukiko;Yabuta, Yukihiro;Saitou, Mitinori
从多能干细胞（PSC）体外诱导和扩增精原干细胞（SSCs）是生殖科学的一个关键目标。我们在这里表明，当与胚胎睾丸体细胞（重组睾丸）聚集时，从小鼠胚胎干细胞诱导的原始生殖细胞样细胞（PGCLC）在体外分化为精原细胞样细胞，并可扩展为类似于生殖系干细胞（GSC）的细胞，一种具有SSC活性的原代细胞系。值得注意的是，GSC样细胞（GSCLC），而不是PGCLC，定殖成年睾丸，虽然不如GSC有效，但有助于精子发生和生育后代。全基因组分析表明，GSCLC在脆弱的调控元件上表现出异常甲基化，包括那些对精子发生至关重要的调控元件，这可能会抑制其生精潜力。我们的研究建立了一个策略，在体外衍生SSC活性从PSC，我们建议，依赖于忠实的表观基因组调控。
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.