Self-organized amniogenesis by human pluripotent stem cells in a biomimetic implantation-like niche.
Self-organized amniogenesis by human pluripotent stem cells in a biomimetic implantation-like niche.
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DOI：
10.1038/nmat4829
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发表时间：
2017-04
期刊：
影响因子：
41.2
通讯作者：
Fu J
中科院分区：
文献类型：
--
作者：
Shao Y;Taniguchi K;Gurdziel K;Townshend RF;Xue X;Yong KMA;Sang J;Spence JR;Gumucio DL;Fu J
羊膜发生--羊膜的发育--是人类早期胚胎发生和成功妊娠的关键发育里程碑。然而，由于获得围着床期胚胎的机会有限，以及缺乏体外模型，人们对人类羊膜发生知之甚少。在这里，我们报道了一种高效的生物材料系统，通过在模拟体内植入环境的生物工程利基中自组织培养人多能干细胞(HPSCs)，在体外产生人羊膜样组织。我们表明，生物物理生态位因子在自我更新允许的生化条件下，充当切换hPSC自我更新和羊膜发生的开关。我们鉴定了hPSC来源的羊膜样细胞的一个独特的分子特征，并表明内源性激活的BMP-SMAD信号是hPSC发育羊膜样组织所必需的。本研究揭示了人类羊膜发生的自组织和机械敏感的本质，并建立了第一个基于hPSC的模型来研究人羊膜围着床期的发育，从而有助于促进人类胚胎学和生殖医学的发展。
Amniogenesis—the development of amnion—is a critical developmental milestone for early human embryogenesis and successful pregnancy,. However, human amniogenesis is poorly understood due to limited accessibility to peri-implantation embryos and a lack ofin vitromodels. Here we report an efficient biomaterial system to generate human amnion-like tissuein vitrothrough self-organized development of human pluripotent stem cells (hPSCs) in a bioengineered niche mimicking thein vivoimplantation environment. We show that biophysical niche factors act as a switch to toggle hPSC self-renewal versus amniogenesis under self-renewal-permissive biochemical conditions. We identify a unique molecular signature of hPSC-derived amnion-like cells and show that endogenously activated BMP–SMAD signalling is required for the amnion-like tissue development by hPSCs. This study unveils the self-organizing and mechanosensitive nature of human amniogenesis and establishes the first hPSC-based model for investigating peri-implantation human amnion development, thereby helping advance human embryology and reproductive medicine.