ATRA induces the differentiation of hepatic progenitor cells by upregulating microRNA-200a

  • Chaoqun Hu
  • Xiaohua Liang
  • Shuyu Fang
  • Lei Xu
  • Mengjia Gong
  • Yi Wang
  • Yang Bi
  • Siqi HongEmail author
  • Yun HeEmail author


Hepatic progenitor cells (HPCs) are potential seed cells for hepatocyte transplantation treatment of liver diseases. ATRA can induce the differentiation and mature function of hepatic progenitor cells, but the mechanism is still poorly understood. Here, by using microRNA array to analyze the expression profiles of microRNA (miR), we found that miR-200 family molecules in HPCs were upregulated after ATRA treatment, especially miR-200a-3p, 200c-3p, and 141-3p. ATRA induction could downregulate the expression of hepatic stem markers Oct4 and AFP, and improve the expression of hepatic markers ALB, CK18, and TAT, and the activity of ALB-GLuc, as well as indocyanine green uptake and glycogen storage function of HPCs. These above effects of ATRA on HPC differentiation were almost inhibited by blocking of miR-200a-3p, but not miR-200c-3p and 141-3p using antagomir. Cell autophagy is associated with ATRA regulation in HPCs, compared with control group, the expression of LC3 and Beclin1 increased in ATRA-treated HPCs, and orange and red fluorescent spot, which represents autophagy flow, also enhanced after ATRA treatment. However, ATRA-induced cell autophagy level was inhibited in antagomir-200a-3p+ATRA-treated cells. Therefore, the present study indicates that antagomir-200a-3p is related to ATRA-induced hepatic differentiation of HPCs through regulating cell autophagy, supporting the possible use of ATRA as a key inducer in HPC-based therapy of liver diseases.


ATRA MicroRNA-200 Hepatic differentiation Antagomir Autophagy 


Funding information

The present study was supported by research grants from the Natural Science Foundation of Chongqing City Grant (No. csct2016jcyjA0228 to YB, cstc2018jcyjAX0111 to YH).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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ESM 1 (DOCX 19 kb)
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Supplementary Figure 1

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High resolution image (TIF 2220 kb)


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Copyright information

© The Society for In Vitro Biology 2019

Authors and Affiliations

  • Chaoqun Hu
    • 1
  • Xiaohua Liang
    • 1
  • Shuyu Fang
    • 1
  • Lei Xu
    • 2
  • Mengjia Gong
    • 1
  • Yi Wang
    • 1
  • Yang Bi
    • 1
  • Siqi Hong
    • 1
    Email author
  • Yun He
    • 1
    Email author
  1. 1.Stem Cell Biology and Therapy Laboratory, Department of Pediatric Surgery, Ministry of Education Key Laboratory of Child Development and DisordersThe Children’s Hospital of Chongqing Medical UniversityChongqingPeople’s Republic of China
  2. 2.Department of MicrobiologyChongqing Medical UniversityChongqingPeople’s Republic of China

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