Genetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6.
Genetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6.
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DOI：
10.1038/ncomms10243
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发表时间：
2016-01-06
影响因子：
16.6
通讯作者：
Weiss R
中科院分区：
文献类型：
--
作者：
Guye P;Ebrahimkhani MR;Kipniss N;Velazquez JJ;Schoenfeld E;Kiani S;Griffith LG;Weiss R
人类诱导多能干细胞（hiPSC）具有个性化和再生医学的潜力。虽然使用这些细胞的大多数方法集中于衍生特化细胞的同质群体，但在产生hiPSC衍生的器官型组织或类器官方面取得了适度的成功。在这里，我们提出了一种新的方法，用于产生，然后共分化hiPSC衍生的祖细胞。随着GATA结合蛋白6（GATA6）表达的基因工程脉冲，我们启动了所有三个胚层的快速出现，作为GATA6表达水平和组织环境的复杂功能。在2周内，我们获得了一个复杂的组织，重现早期发育过程，并表现出肝芽样表型，包括造血和基质细胞以及神经元生态位。总的来说，我们的方法证明了使用单一自体hiPSC作为来源从hiPSC衍生复杂组织，并产生一系列与实质细胞共同发育以形成组织的基质细胞。 从人诱导多能干细胞（hiPSC）产生组织的成功有限。在这里，作者对转录因子Gata 6在单个同基因hiPSC群体中的表达进行了基因工程，产生了表现出肝芽样特性的复杂组织结构。
Human induced pluripotent stem cells (hiPSCs) have potential for personalized and regenerative medicine. While most of the methods using these cells have focused on deriving homogenous populations of specialized cells, there has been modest success in producing hiPSC-derived organotypic tissues or organoids. Here we present a novel approach for generating and then co-differentiating hiPSC-derived progenitors. With a genetically engineered pulse of GATA-binding protein 6 (GATA6) expression, we initiate rapid emergence of all three germ layers as a complex function of GATA6 expression levels and tissue context. Within 2 weeks we obtain a complex tissue that recapitulates early developmental processes and exhibits a liver bud-like phenotype, including haematopoietic and stromal cells as well as a neuronal niche. Collectively, our approach demonstrates derivation of complex tissues from hiPSCs using a single autologous hiPSCs as source and generates a range of stromal cells that co-develop with parenchymal cells to form tissues. There has been limited success in generating tissues from human induced pluripotent stem cells (hiPSCs). Here, the authors genetically engineer expression of the transcription factor Gata6 in a single isogenic hiPSC population resulting in complex tissue structures that exhibit liver bud-like properties.