期刊
AGING-US
卷 9, 期 5, 页码 1359-1374出版社
IMPACT JOURNALS LLC
DOI: 10.18632/aging.101232
关键词
aging; stem cells; liver regeneration; neutrophil; reactive oxygen species
资金
- Ministry of Science and Technology of China [2015CB943300, 2011CB966200, 2014CB943300]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA01040000]
- National Natural Science Foundation of China [81130057, 81373164, 31300708, 81471217]
- Program of Science and Technology Commission of Shanghai Municipality [14ZR1446300, 13ZR1423200, 12ZR1415900]
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.
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