小柯机器人

近日，日本京都大学Mitinori Saitou团队利用小鼠多能干细胞实现整个雄性生殖细胞发育过程的体外重组。相关论文于2021年9月7日在线发表在《细胞—干细胞》杂志上。

研究人员实现了多能干细胞（PSC）对整个雄性生殖细胞发育的体外重建。小鼠胚胎干细胞（mESC）被诱导成PGC样细胞（mPGCLC），这些细胞被扩增用于表观遗传重编程。在优化条件下重建的睾丸中，这种mPGCLC分化为精原细胞样细胞，并具有适当的发育过渡、基因表达和细胞周期动态，并进一步被扩增为生殖干细胞样细胞（GSCLC），且具有适当的雄性基因表观组。

重要的是，GSCLC显示出旺盛的精子生成能力，不仅在移植到体内睾丸后，而且在体外睾丸移植培养下，所产生的精子为可育后代作出贡献。通过对雄性生殖细胞发育三个阶段的忠实再现，这项研究为PSC的体外雄性配子发生建立了一个范式。

据了解，哺乳动物的雄性生殖细胞发育包括三个不同的阶段：原始生殖细胞（PGC）的发育、雄性生殖细胞的精原细胞发育分化以及随后的精子发生。

附：英文原文

Title: In vitro reconstitution of the whole male germ-cell development from mouse pluripotent stem cells

Author: Yukiko Ishikura, Hiroshi Ohta, Takuya Sato, Yusuke Murase, Yukihiro Yabuta, Yoji Kojima, Chika Yamashiro, Tomonori Nakamura, Takuya Yamamoto, Takehiko Ogawa, Mitinori Saitou

Issue&Volume: September 07, 2021

Abstract: Mammalian male germ-cell development consists of three distinct phases: primordialgerm cell (PGC) development, male germ-cell specification for spermatogonium development,and ensuing spermatogenesis. Here, we show an in vitro reconstitution of whole male germ-cell development by pluripotent stem cells (PSCs).Mouse embryonic stem cells (mESCs) are induced into PGC-like cells (mPGCLCs), whichare expanded for epigenetic reprogramming. In reconstituted testes under an optimizedcondition, such mPGCLCs differentiate into spermatogonium-like cells with proper developmentaltransitions, gene expression, and cell-cycle dynamics and are expanded robustly asgermline stem cell-like cells (GSCLCs) with an appropriate androgenetic epigenome.Importantly, GSCLCs show vigorous spermatogenesis, not only upon transplantation intotestes in vivo but also under an in vitro culture of testis transplants, and the resultant spermatids contribute to fertileoffspring. By uniting faithful recapitulations of the three phases of male germ-celldevelopment, our study creates a paradigm for the in vitro male gametogenesis by PSCs.

DOI: 10.1016/j.stem.2021.08.005

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00342-8

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