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首页> 外文期刊>Journal of Cellular Physiology >Differences in definitive endoderm induction approaches using growth factors and small molecules
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Differences in definitive endoderm induction approaches using growth factors and small molecules

机译：差异的内胚层归纳方法使用生长因子和小分子

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摘要

Definitive endoderm (DE) is the first stage of human pluripotent stem cell (hPSC) differentiation into hepatocyte‐like cells. Developing human liver cell models for pharmaceutical applications is highly demanding. Due to the vast number of existing protocols to generate DE cells from hPSCs, we aimed to compare the specificity and efficiency of selected published differentiation conditions. We differentiated two hPSC lines (induced PSC and embryonic stem cell) to DE cells on Matrigel matrix using growth factors (Activin A and Wnt‐3a) and small molecules (sodium butyrate and IDE 1) in different combinations. By studying dynamic changes during 6 days in cell morphology and the expression of markers for pluripotency, DE, and other germ layer lineages, we found that Activin A is essential for DE differentiation, while Wnt‐3a and sodium butyrate are dispensable. Although sodium butyrate exerted rapid DE differentiation kinetics, it caused massive cell death and could not generate sufficient cells for further differentiation and applications. We further discover that IDE 1 could not induce DE as reported previously. Hereby, we compared different conditions for DE induction and found an effective six day‐protocol to obtain DE cells for the further differentiation and applications.
机译：明确的内胚层(DE)的第一阶段人类多能干细胞(hPSC)分化成肝细胞类细胞。发展人类肝细胞模型制药应用程序高度要求。由于大量的现有的协议从hPSCs生成DE细胞,我们旨在比较选择的专一性和效率发表的分化情况。(PSC诱导和分化两个hPSC行胚胎干细胞)DE细胞基底膜基质矩阵使用生长因子(激活素A和Wnt量3)和小分子(丁酸钠和IDE 1)在不同的组合。在6天在细胞形态学动态变化和多能性标记物的表达,德和其他细菌层血统,我们发现苯丙酸诺龙DE分化是至关重要的,而地理Wnt 3 a和丁酸钠是可有可无的。尽管丁酸钠对快速DE微分动力学,它造成巨大细胞死亡并不能产生足够的细胞进一步分化和应用程序。进一步发现IDE 1不能诱导DE先前报道。DE感应,发现不同的条件一个有效的六日协议获得细胞为进一步分化和应用程序。

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