MicroRNA Regulates Hepatocytic Differentiation of Progenitor Cells by Targeting YAP1.
MicroRNA Regulates Hepatocytic Differentiation of Progenitor Cells by Targeting YAP1.
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DOI：
10.1002/stem.2283
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发表时间：
2016-05
期刊：
影响因子：
--
通讯作者：
Beretta L
中科院分区：
文献类型：
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作者：
Jung KH;McCarthy RL;Zhou C;Uprety N;Barton MC;Beretta L
在肝细胞分化后人肝祖细胞中的microRNA表达谱鉴定miR-122和miR-194为在祖细胞的肝细胞分化期间最强烈上调的microRNA。miR-194在人胚胎干细胞（hESC）的肝细胞分化后也高度上调。miR-194在祖细胞中的过表达加速了它们向肝细胞的分化，如通过形态学特征如小管和肝细胞标志物的表达所测量的。miR-194在hESC中的过表达诱导了它们的自发分化，这是一种伴随多能因子OCT 4和NANOG的加速丧失以及中胚层标记物HAND 1表达降低的表型。然后，我们将YAP 1鉴定为miR-194的直接靶点。抑制YAP 1强烈诱导祖细胞的肝细胞分化，并且YAP 1过表达逆转了miR-194诱导的祖细胞的肝细胞分化。总之，我们鉴定了miR-194作为祖细胞的肝细胞分化的有效诱导剂，并进一步鉴定了YAP 1作为miR-194对肝细胞分化和肝祖细胞命运的影响的介体。
MicroRNA expression profiling in human liver progenitor cells following hepatocytic differentiation identified miR-122 and miR-194 as the microRNAs most strongly upregulated during hepatocytic differentiation of progenitor cells. MiR-194 was also highly upregulated following hepatocytic differentiation of human embryonic stem cells (hESCs). Overexpression of miR-194 in progenitor cells accelerated their differentiation into hepatocytes, as measured by morphological features such as canaliculi and expression of hepatocytic markers. Overexpression of miR-194 in hESCs induced their spontaneous differentiation, a phenotype accompanied with accelerated loss of the pluripotent factors OCT4 and NANOG and decrease in mesoderm marker HAND1 expression. We then identified YAP1 as a direct target of miR-194. Inhibition of YAP1 strongly induced hepatocytic differentiation of progenitor cells and YAP1 over expression reversed the miR-194-induced hepatocytic differentiation of progenitor cells. In conclusion, we identified miR-194 as a potent inducer of hepatocytic differentiation of progenitor cells and further identified YAP1 as a mediator of miR-194's effects on hepatocytic differentiation and liver progenitor cell fate.