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Cell:成功通过iPS细胞繁育出老鼠

日本京都大学教授齐藤通纪领衔的科研小组在4日的美国《细胞》杂志网络版上宣布,通过人造多功能干细胞(iPS细胞)制作的精子与卵子体外受精后繁育老鼠的研究取得了成功。

由雄性老鼠的细胞制作的iPS细胞在试管内分化为生殖细胞,成为生成精子和卵子的原始细胞。通过利用iPS细胞制作生殖细胞并成功培育出生命在全球尚属首例。

科研小组认为,此次突破将有助于阐明生物的形成和人类生殖细胞的详细发展过程,揭开不孕症的原因并推动治疗。由于这一技术涉及到制作人类生殖细胞,或将引发生命伦理方面的热议。

研究小组把通过雄性幼鼠的纤维芽细胞制作的iPS细胞加入蛋白质和其他制剂进行培养,制作出接近多功能细胞集团的细胞。这一细胞在其他蛋白质的刺激下生成了生殖细胞。

生殖细胞被植入无生殖细胞的雄性老鼠的精巢后,用大约10周时间生成精子。生成的精子与卵子完成体外受精后,受精卵被放回雌性老鼠体内,成功繁育出了健康的雄性和雌性鼠崽。这些老鼠与普通老鼠交配后也生出了下一代。

 

英文论文摘要:

Reconstitution of the Mouse Germ Cell Specification Pathway in Culture by Pluripotent Stem Cells

Highlights

Generation of primordial germ cell-like cells (PGCLCs) from ESCs and iPSCs

PGCLC induction occurs via an epiblast-like state, mimicking PGC generation in vivo

PGCLCs contribute to spermatogenesis and produce fertile offspring

Integrin-β3 and SSEA1 mark PGCLCs and allow purification from teratogenic cells

Summary

The generation of properly functioning gametes in vitro requires reconstitution of the multistepped pathway of germ cell development. We demonstrate here the generation of primordial germ cell-like cells (PGCLCs) in mice with robust capacity for spermatogenesis. PGCLCs were generated from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) through epiblast-like cells (EpiLCs), a cellular state highly similar to pregastrulating epiblasts but distinct from epiblast stem cells (EpiSCs). Reflecting epiblast development, EpiLC induction from ESCs/iPSCs is a progressive process, and EpiLCs highly competent for the PGC fate are a transient entity. The global transcription profiles, epigenetic reprogramming, and cellular dynamics during PGCLC induction from EpiLCs meticulously capture those associated with PGC specification from the epiblasts. Furthermore, we identify Integrin-β3 and SSEA1 as markers that allow the isolation of PGCLCs with spermatogenic capacity from tumorigenic undifferentiated cells. Our findings provide a paradigm for the first step of in vitro gametogenesis.

 

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摘要
日本京都大学教授齐藤通纪领衔的科研小组在4日的美国《细胞》杂志网络版上宣布,通过人造多功能干细胞(iPS细胞)制作的精子与卵子体外受精后繁育老鼠的研究取得了成功。
关键字
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