Small molecules efficiently direct endodermal differentiation of mouse and human embryonic stem cells.
Small molecules efficiently direct endodermal differentiation of mouse and human embryonic stem cells.
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DOI：
10.1016/j.stem.2009.01.014
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发表时间：
2009-04-03
期刊：
影响因子：
23.9
通讯作者：
Melton DA
中科院分区：
文献类型：
--
作者：
Borowiak M;Maehr R;Chen S;Chen AE;Tang W;Fox JL;Schreiber SL;Melton DA
干细胞治疗和研究应用的一个重要步骤是将它们分化为特定细胞类型的能力。包括肺、肝和胰腺在内的内皮细胞衍生物对再生医学很有兴趣，但生产这些细胞的努力只取得了一定的成功。在4000个化合物的筛选中，鉴定出两个细胞通透性小分子，它们直接将ESCs分化为内胚层。这些化合物诱导近80%的胚胎干细胞形成最终的内胚层，比常用的内胚层蛋白诱导剂激活素A或Nodal的效率更高。化学诱导的内胚层表达多种内胚层标志物，注入胚胎肠管后可参与正常发育，体外可形成胰岛祖细胞。应用小分子将小鼠和人的胚胎干细胞分化为内胚层和胰岛前体细胞，代表着朝着实现可重复和高效生产所需ES细胞衍生物的方向迈出了一步。
An essential step for therapeutic and research applications of stem cells is the ability to differentiate them into specific cell types. Endodermal cell derivatives, including lung, liver and pancreas, are of interest for regenerative medicine, but efforts to produce these cells have been met with only modest success. In a screen of 4000 compounds, two cell permeable small molecules were indentified that direct differentiation of ESCs into the endodermal lineage. These compounds induce nearly 80% of ESCs to form definitive endoderm, a higher efficiency than that achieved with Activin A or Nodal, commonly used protein inducers of endoderm. The chemically induced endoderm expresses multiple endodermal markers, can participate in normal development when injected into the embryonic gut tube and can form pancreatic progenitors in vitro. The application of small molecules to differentiate mouse and human ESCs into endoderm, and pancreatic progenitors represents a step toward achieving a reproducible and efficient production of desired ES cell derivatives.