title: MicroRNA Regulates Hepatocytic Differentiation of Progenitor Cells by Targeting YAP1.
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. Stem Cells 2016;34:1284-1296.
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Kwang Hwa
authors.initials: KH
authors.lastname: Jung
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ryan L
authors.initials: RL
authors.lastname: McCarthy
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Chong
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Nadima
authors.initials: N
authors.lastname: Uprety
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, USA.
authors.forename: Michelle Craig
authors.initials: MC
authors.lastname: Barton
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Beretta
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism*; D000066449:Human Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000166:cytology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D014157:Transcription Factors; D015854:Up-Regulation / Q000235:genetics; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C554846:MIRN194 microRNA, human; D035683:MicroRNAs; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human
keywords: Differentiation; Hepatocytes; Progenitor cells; YAP1; miR-194