期刊
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
卷 36, 期 3, 页码 1163-1174出版社
KARGER
DOI: 10.1159/000430287
关键词
Autophagy; Self-renewal; Hepatic differentiation; Cellular senescence
资金
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA01040000]
- Ministry of Science and Technology of China [2011CB966200, 2014CB943300]
- National Natural Science Foundation of China [81130057, 81071748, 81373164, 81190133, 31300708]
- Program of Science and Technology Commission of Shanghai Municipality [12ZR1415900, 13ZR1423200, 14ZR1446300]
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. Copyright (C) 2015 S. Karger AG, Basel
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