MicroRNA regulates hepatocytic differentiation of progenitor cells by targeting YAP1

KH Jung, RL McCarthy, C Zhou, N Uprety… - Stem Cells, 2016 - academic.oup.com
KH Jung, RL McCarthy, C Zhou, N Uprety, MC Barton, L Beretta
Stem Cells, 2016academic.oup.com
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 …
Abstract
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 overexpression 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.
Oxford University Press
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