Differentiation of hepatocyte-like cells from human pluripotent stem cells using small molecules.
Differentiation of hepatocyte-like cells from human pluripotent stem cells using small molecules.
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DOI：
10.1016/j.diff.2018.03.002
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Schiff ER
中科院分区：
文献类型：
--
作者：
Asumda FZ;Hatzistergos KE;Dykxhoorn DM;Jakubski S;Edwards J;Thomas E;Schiff ER
已经开发了多种用于从多能干细胞衍生肝细胞样细胞的方法。目前，大多数这些策略采用逐步分化的方法与重组生长因子或小分子类似物重演发育信号通路。在这里，我们测试了基于小分子的分化方案从人多能干细胞生成肝细胞样细胞的功效。SOX 17、FOXA 2、CXCR 4、HNF 4A、AFP的定量基因表达、免疫组织化学和蛋白质印迹分析表明，阶段特异性分化为定形内胚层、成肝细胞和肝细胞样衍生物。此外，肝细胞样细胞显示出原代肝细胞的形态和功能特征，如ALB（白蛋白）和α-1-抗胰蛋白酶（A1 AT）的产生以及通过过碘酸-希夫染色的糖原储存能力所示。总之，这些数据支持基于小分子的肝分化方案是一种简单、可重复且廉价的方法，可有效驱动人多能干细胞向肝细胞样表型分化，用于下游药物基因组学和再生医学应用。
A variety of approaches have been developed for the derivation of hepatocyte-like cells from pluripotent stem cells. Currently, most of these strategies employ step-wise differentiation approaches with recombinant growth-factors or small-molecule analogs to recapitulate developmental signaling pathways. Here, we tested the efficacy of a small-molecule based differentiation protocol for the generation of hepatocyte-like cells from human pluripotent stem cells. Quantitative gene-expression, immunohistochemical, and western blot analyses for SOX17, FOXA2, CXCR4, HNF4A, AFP, indicated the stage-specific differentiation into definitive endoderm, hepatoblast and hepatocyte-like derivatives. Furthermore, hepatocyte-like cells displayed morphological and functional features characteristic of primary hepatocytes, as indicated by the production of ALB (albumin) and α-1-antitrypsin (A1AT), as well as glycogen storage capacity by periodic acid-Schiff staining. Together, these data support that the small-molecule based hepatic differentiation protocol is a simple, reproducible, and inexpensive method to efficiently drive the differentiation of human pluripotent stem cells towards a hepatocyte-like phenotype, for downstream pharmacogenomic and regenerative medicine applications.
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影响因子：
4.8
作者：
Sa-Ngiamsuntorn K;Wongkajornsilp A;Phanthong P;Borwornpinyo S;Kitiyanant N;Chantratita W;Hongeng S
通讯作者：
Hongeng S
影响因子：
5.4
作者：
Breiman, A;Grandvaux, N;Meurs, EF
通讯作者：
Meurs, EF
干细胞衍生的模型，以提高对人类药物诱导的肝损伤的机械理解和预测。
DOI：
10.1002/hep.28886
发表时间：
2017-02
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Goldring C;Antoine DJ;Bonner F;Crozier J;Denning C;Fontana RJ;Hanley NA;Hay DC;Ingelman-Sundberg M;Juhila S;Kitteringham N;Silva-Lima B;Norris A;Pridgeon C;Ross JA;Young RS;Tagle D;Tornesi B;van de Water B;Weaver RJ;Zhang F;Park BK
通讯作者：
Park BK
影响因子：
23.9
作者：
Borowiak M;Maehr R;Chen S;Chen AE;Tang W;Fox JL;Schreiber SL;Melton DA
通讯作者：
Melton DA
影响因子：
4.6
作者：
Engert, Silvia;Burtscher, Ingo;Lickert, Heiko
通讯作者：
Lickert, Heiko