Metastable primordial germ cell-like state induced from mouse embryonic stem cells by Akt activation

Metastable primordial germ cell-like state induced from mouse embryonic stem cells by Akt activation
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DOI:
10.1016/j.bbrc.2010.01.005
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发表时间:
2010-02-12
影响因子:
3.1
通讯作者:
Nakano, Toru
Nakano, Toru
中科院分区:
生物学4区
文献类型:
--
作者:
Yamano, Noriko;Kimura, Tohru;Nakano, Toru

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原肠发育过程中中胚层诱导信号介导了原始生殖细胞(PGCs)的分化。我们发现,在胚胎干细胞(ESCs)体外中胚层分化过程中,Akt的激活产生了分化状态介于ESCs和PGCs之间的自我更新球体,其下游生殖细胞特异性基因在球体中表达,表明球状细胞已经开始向生殖系分化。然而,在移植到睾丸球体后,将细胞转移到原始的无饲养层的ESC培养上,在小鼠胚胎成纤维细胞上培养或在ERK-Casade和GSK3抑制剂的存在下,这些球体不能进行精子发生。这些结果表明Akt信号促进了一种介于ESCs和PGCs之间的新的亚稳态和潜在的状态。(C)2010爱思唯尔公司版权所有。
Specification to primordial germ cells (PGCs) is mediated by mesoderm-induction signals during gastrulation We found that Akt activation during in vitro mesodermal differentiation of embryonic stem cells (ESCs) generated self-renewing spheres with differentiation states between those of ESCs and PGCs Essential regulators for PGC specification and their downstream germ cell-specific genes were expressed in the spheres, indicating that the sphere cells had commenced differentiation to the germ lineage. However, the spheres did not proceed to spermatogenesis after transplantation into testes Sphere cell transfer to the original feeder-free ESC Cultures resulted in chaotic differentiation in contrast, when the spheres were cultured on mouse embryonic fibroblasts or in the presence of ERK-cascade and GSK3 inhibitors. reversion to the ESC-like state was observed These results indicate that Akt signaling promotes a novel metastable and plunpotent state that is intermediate to those of ESCs and PGCs. (C) 2010 Elsevier Inc All rights reserved.