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Hepatology. 2016 Jul;64(1):245-60. doi: 10.1002/hep.28548. Epub 2016 Apr 15.

Suppression of lethal-7b and miR-125a/b Maturation by Lin28b Enables Maintenance of Stem Cell Properties in Hepatoblasts.

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  • 1Division of Organogenesis and Regeneration, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
  • 2Core Research for Evolutional Science and Technology, The Japan Agency for Medical Research and Development, Chiyoda-ku, Tokyo, Japan.


In liver development, hepatoblasts that act as hepatic stem/progenitor cells proliferate and differentiate into both hepatocytes and cholangiocytes to form liver tissues. Although numerous factors contribute to this event, little is known about the roles of microRNAs in hepatoblast proliferation and differentiation. In this study, we focused on the lineage-28 (Lin28) family proteins, which are required for microRNA regulation in pluripotent stem cells and cancer cells, and investigated their roles as regulatory factors for the properties of hepatoblasts.


Lin28b was specifically expressed in hepatoblasts, and its suppression induced growth arrest and cholangiocyte differentiation of hepatoblasts; mechanistically, Lin28b positively regulates the expression of Lin28b itself and cell cycle-related proteins in hepatoblasts by suppressing the maturation of target microRNAs, lethal-7b and miR-125a/b, enabling maintenance of the stem cell properties of hepatoblasts, such as their capabilities for proliferation and bi-lineage differentiation, during liver development. (Hepatology 2016;64:245-260).

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