Details

Autor(en) / Beteiligte

• Pan, Huize
• Guan, Di
• Liu, Xiaomeng
• Li, Jingyi
• Wang, Lixia
• Wu, Jun
• Zhou, Junzhi
• Zhang, Weizhou
• Ren, Ruotong
• Zhang, Weiqi
• Li, Ying
• Yang, Jiping
• Hao, Ying
• Yuan, Tingting
• Yuan, Guohong
• Wang, Hu
• Ju, Zhenyu
• Mao, Zhiyong
• Li, Jian
• Qu, Jing
• Tang, Fuchou
• Liu, Guang-Hui

Titel

SIRT6 safeguards human mesenchymal stem cells from oxidative stress by coactivating NRF2

Ist Teil von

• Cell research, 2016-02, Vol.26 (2), p.190-205

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• SIRT6 belongs to the mammalian homologs of Sir2 histone NAD＋-dependent deacylase family. In rodents, SIRT6 deficiency leads to aging-associated degeneration of mesodermal tissues. It remains unknown whether human SIRT6 has a direct role in maintaining the homeostasis of mesodermal tissues. To this end, we generated SIRT6 knockout hu- man mesenchymal stem cells （hMSCs） by targeted gene editing. SIRT6-deficient hMSCs exhibited accelerated func- tional decay, a feature distinct from typical premature cellular senescence. Rather than compromised chromosomal stability, SIRT6-null hMSCs were predominately characterized by dysregulated redox metabolism and increased sen- sitivity to the oxidative stress. In addition, we found SIRT6 in a protein complex with both nuclear factor erythroid 2-related factor 2 （NRF2） and RNA polymerase II, which was required for the transactivation of NRF2-regulated an- tioxidant genes, including heme oxygenase 1 （HO-1）. Overexpression of HO-1 in SIRT6-null hMSCs rescued prema- ture cellular attrition. Our study uncovers a novel function of SIRT6 in maintaining hMSC homeostasis by serving as a NRF2 coactivator, which represents a new layer of regulation of oxidative stress-associated stem cell decay.