Research Paper Volume 9, Issue 5 pp 1359—1374

Aging-associated oxidative stress inhibits liver progenitor cell activation in mice

Yiji Cheng 1, *, , Xue Wang 1, *, , Bei Wang 2, , Hong Zhou 2, , Shipeng Dang 2, , Yufang Shi 2, , Li Hao 3, , Qingquan Luo 1, , Min Jin 2, , Qianjun Zhou 1, , Yanyun Zhang 1, 2, ,

  • 1 Shanghai Institute of Immunology and Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • 2 Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • 3 Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, China
* Equal contribution

received: April 1, 2017 ; accepted: April 23, 2017 ; published: April 29, 2017 ;
How to Cite

Copyright: Cheng et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Recent studies have discovered aging-associated changes of adult stem cells in various tissues and organs, which potentially contribute to the organismal aging. However, aging-associated changes of liver progenitor cells (LPCs) remain elusive. Employing young (2-month-old) and old (24-month-old) mice, we found diverse novel alterations in LPC activation during aging. LPCs in young mice could be activated and proliferate upon liver injury, whereas the counterparts in old mice failed to respond and proliferate, leading to the impaired liver regeneration. Surprisingly, isolated LPCs from young and old mice did not exhibit significant difference in their clonogenic and proliferative capacity. Later, we uncovered that the decreased activation and proliferation of LPCs were due to excessive reactive oxygen species produced by neutrophils infiltrated into niche, which was resulted from chemokine production from activated hepatic stellate cells during aging. This study demonstrates aging-associated changes in LPC activation and reveals critical roles for the stem cell niche, including neutrophils and hepatic stellate cells, in the negative regulation of LPCs during aging.


LPCs: liver progenitor cells; ROS: reactive oxygen species; AFP: α-fetoprotein; CK19: cytokeratin 19; EpCAM: epithelial cell adhesion molecule; MDA: malondialdehyde; CDE diet: choline-deficient, ethionine-supplemented diet; ECM: extracellular matrix.