由 Akt 激活从小鼠胚胎干细胞中诱导出的亚稳定原始生殖细胞样状态。

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

机构信息

Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.

出版信息

Biochem Biophys Res Commun. 2010 Feb 12;392(3):311-6. doi: 10.1016/j.bbrc.2010.01.005. Epub 2010 Jan 6.

DOI:10.1016/j.bbrc.2010.01.005

PMID:20059970

Abstract

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 pluripotent state that is intermediate to those of ESCs and PGCs.

摘要

原始生殖细胞（PGCs）的特化是由原肠胚形成过程中的中胚层诱导信号介导的。我们发现，胚胎干细胞（ESCs）在体外中胚层分化过程中 Akt 的激活会产生具有自我更新能力的球体，其分化状态介于 ESCs 和 PGCs 之间。PGC 特化的必需调控因子及其下游的生殖细胞特异性基因在球体中表达，表明球体细胞已开始向生殖系分化。然而，这些球体在移植到睾丸后并没有进行精子发生。将球体细胞转移到原始无饲养层 ESC 培养物中会导致混乱的分化。相比之下，当球体在小鼠胚胎成纤维细胞上或在 ERK 级联和 GSK3 抑制剂存在的情况下培养时，会观察到向 ESC 样状态的逆转。这些结果表明 Akt 信号促进了一种新颖的亚稳态和多能性状态，该状态介于 ESCs 和 PGCs 之间。