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

被引：1034

作者：

Hayashi, Katsuhiko ^{[1
,3
]}

Ohta, Hiroshi ^{[1
,3
]}

Kurimoto, Kazuki ^{[1
,3
]}

Aramaki, Shinya ^{[1
]}

Saitou, Mitinori ^{[1
,2
,3
]}

机构：

[1] Kyoto Univ, Grad Sch Med, Dept Anat & Cell Biol, Sakyo Ku, Kyoto 6068501, Japan

[2] Kyoto Univ, Inst Integrated Cell Mat Sci, Sakyo Ku, Kyoto 6068501, Japan

[3] CREST, JST, Sakyo Ku, Kyoto 6068501, Japan

来源：

CELL | 2011年 / 146卷 / 04期

关键词：

GROUND-STATE; MICE; GENERATION; EPIBLAST; LINEAGE; EMBRYOS; TRANSPLANTATION; ESTABLISHMENT; BLIMP1; TESTIS;

D O I：

10.1016/j.cell.2011.06.052

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-beta 3 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.

引用

页码：519 / 532

页数：14

共 41 条

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Cohen, Philip ;

Smith, Austin .

NATURE, 2008, 453 (7194) :519-U5

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