Open AccessMicroRNA Regulates Hepatocytic Differentiation of Progenitor Cells by Targeting YAP 1
Author(s) -
Jung Kwang Hwa,
McCarthy Ryan L.,
Zhou Chong,
Uprety Nadima,
Barton Michelle Craig,
Beretta Laura
Publication year - 2016
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2283
Subject(s) - progenitor cell , biology , microbiology and biotechnology , cellular differentiation , embryonic stem cell , progenitor , stem cell , mesoderm , yap1 , homeobox protein nanog , induced pluripotent stem cell , transcription factor , genetics , gene
A bstract 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. S tem C ells 2016;34:1284–1296