Autophagy is Required for the Maintenance of Liver Progenitor Cell Functionality

Yiji Cheng, Bei Wang, Hong Zhou, Shipeng Dang, Min Jin, Yufang Shi, Li Hao, Zhenxi Yang, Yanyun Zhang

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Background: Liver progenitor cells (LPCs) are bipotent stem cells existing in the adult liver, which could be activated upon massive liver injury and contribute to liver regeneration. However, mechanisms of maintenance of LPC functionality remain poorly understood. Previous studies found that autophagy was required for the self-renewal and differentiation of several tissue stem cells. Methods: The study compared the level of autophagic activity in LPCs and differentiated hepatocytes. Then, autophagic activity was inhibited in LPCs by lentivirus-mediated autophagy-related gene 5 or Beclin 1 knockdown. Clonogenic assay, cell viability assays, hepatic differentiation assay, and senescence analysis were conducted to assess the role of autophagy in regulating self-renewal, hepatic differentiation and senescence of LPCs. Results: We observed high autophagic activity in LPCs compared with differentiated hepatocytes. We found that inhibition of autophagy impaired the self-renewal, proliferation, and hepatic differentiation capability of LPCs under normal cultural condition, but had little impact on cell viability. Interestingly, while wild-type LPCs remained rarely affected by the toxin, etoposide, inhibition of autophagy induced the senescent phenotype of LPCs. Overexpression of Beclin 1 in Beclin 1-knockdown LPCs restored the functionality of stem cells. Conclusion: Our findings indicate that autophagy may function as a critical regulator of LPC functionality under both physiological and pathological condition.

Original languageEnglish (US)
Pages (from-to)1163-1174
Number of pages12
JournalCellular Physiology and Biochemistry
Volume36
Issue number3
DOIs
StatePublished - Jul 13 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology

Keywords

  • Autophagy
  • Cellular senescence
  • Hepatic differentiation
  • Self-renewal

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