PMID- 26768768
OWN - NLM
STAT- MEDLINE
DCOM- 20161026
LR  - 20240213
IS  - 1748-7838 (Electronic)
IS  - 1001-0602 (Print)
IS  - 1001-0602 (Linking)
VI  - 26
IP  - 2
DP  - 2016 Feb
TI  - SIRT6 safeguards human mesenchymal stem cells from oxidative stress by 
      coactivating NRF2.
PG  - 190-205
LID - 10.1038/cr.2016.4 [doi]
AB  - 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 human mesenchymal stem cells (hMSCs) by targeted gene 
      editing. SIRT6-deficient hMSCs exhibited accelerated functional 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 sensitivity 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 antioxidant genes, including heme oxygenase 
      1 (HO-1). Overexpression of HO-1 in SIRT6-null hMSCs rescued premature 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.
FAU - Pan, Huize
AU  - Pan H
AD  - National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese 
      Academy of Sciences, Beijing 100101, China.
AD  - University of Chinese Academy of Sciences, Beijing 100049, China.
FAU - Guan, Di
AU  - Guan D
AD  - National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese 
      Academy of Sciences, Beijing 100101, China.
FAU - Liu, Xiaomeng
AU  - Liu X
AD  - Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, 
      Beijing 100871, China.
FAU - Li, Jingyi
AU  - Li J
AD  - Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, 
      Beijing 100871, China.
FAU - Wang, Lixia
AU  - Wang L
AD  - National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese 
      Academy of Sciences, Beijing 100101, China.
AD  - FSU-CAS Innovation Institute, Foshan University, Foshan, Guangdong 528000, China.
AD  - State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, 
      Chinese Academy of Sciences, Beijing 100101, China.
FAU - Wu, Jun
AU  - Wu J
AD  - Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 
      92037, USA.
FAU - Zhou, Junzhi
AU  - Zhou J
AD  - National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese 
      Academy of Sciences, Beijing 100101, China.
FAU - Zhang, Weizhou
AU  - Zhang W
AD  - Department of Pathology, Carver College of Medicine, University of Iowa, Iowa 
      City, IA 52242, USA.
FAU - Ren, Ruotong
AU  - Ren R
AD  - National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese 
      Academy of Sciences, Beijing 100101, China.
AD  - FSU-CAS Innovation Institute, Foshan University, Foshan, Guangdong 528000, China.
FAU - Zhang, Weiqi
AU  - Zhang W
AD  - National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese 
      Academy of Sciences, Beijing 100101, China.
AD  - FSU-CAS Innovation Institute, Foshan University, Foshan, Guangdong 528000, China.
FAU - Li, Ying
AU  - Li Y
AD  - National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese 
      Academy of Sciences, Beijing 100101, China.
AD  - University of Chinese Academy of Sciences, Beijing 100049, China.
FAU - Yang, Jiping
AU  - Yang J
AD  - National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese 
      Academy of Sciences, Beijing 100101, China.
FAU - Hao, Ying
AU  - Hao Y
AD  - FSU-CAS Innovation Institute, Foshan University, Foshan, Guangdong 528000, China.
AD  - State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, 
      Chinese Academy of Sciences, Beijing 100101, China.
FAU - Yuan, Tingting
AU  - Yuan T
AD  - National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese 
      Academy of Sciences, Beijing 100101, China.
FAU - Yuan, Guohong
AU  - Yuan G
AD  - National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese 
      Academy of Sciences, Beijing 100101, China.
FAU - Wang, Hu
AU  - Wang H
AD  - Institute of Aging Research, Leibniz Link Partner Group on Stem Cell Aging, 
      Hangzhou Normal University School of Medicine, Hangzhou, Zhejiang 310036, China.
FAU - Ju, Zhenyu
AU  - Ju Z
AD  - Institute of Aging Research, Leibniz Link Partner Group on Stem Cell Aging, 
      Hangzhou Normal University School of Medicine, Hangzhou, Zhejiang 310036, China.
FAU - Mao, Zhiyong
AU  - Mao Z
AD  - School of life sciences and technology, Tongji University, Shanghai 200092, 
      China.
FAU - Li, Jian
AU  - Li J
AD  - The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of 
      Geriatrics, Ministry of Health, Beijing 100730, China.
FAU - Qu, Jing
AU  - Qu J
AD  - State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, 
      Chinese Academy of Sciences, Beijing 100101, China.
FAU - Tang, Fuchou
AU  - Tang F
AD  - Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, 
      Beijing 100871, China.
AD  - Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, 
      Beijing 100871, China.
AD  - Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, 
      China.
AD  - Center for Molecular and Translational Medicine, CMTM, Beijing 100101, China.
FAU - Liu, Guang-Hui
AU  - Liu GH
AD  - National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese 
      Academy of Sciences, Beijing 100101, China.
AD  - FSU-CAS Innovation Institute, Foshan University, Foshan, Guangdong 528000, China.
AD  - Center for Molecular and Translational Medicine, CMTM, Beijing 100101, China.
AD  - Beijing Institute for Brain Disorders, Beijing 100069, China.
LA  - eng
GR  - K99 CA158055/CA/NCI NIH HHS/United States
GR  - P30 CA086862/CA/NCI NIH HHS/United States
GR  - R00 CA158055/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160115
PL  - England
TA  - Cell Res
JT  - Cell research
JID - 9425763
RN  - 0 (Antioxidants)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 2.7.7.- (RNA Polymerase II)
RN  - EC 3.5.1.- (SIRT6 protein, human)
RN  - EC 3.5.1.- (Sirtuins)
SB  - IM
CIN - Cell Res. 2016 Feb;26(2):143-4. PMID: 26780861
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Cells, Cultured
MH  - Cellular Senescence/physiology
MH  - Heme Oxygenase-1/metabolism
MH  - Homeostasis/physiology
MH  - Humans
MH  - Male
MH  - Mesenchymal Stem Cells/*metabolism
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, Nude
MH  - Mice, SCID
MH  - NF-E2-Related Factor 2/*metabolism
MH  - Oxidative Stress/*physiology
MH  - RNA Polymerase II/metabolism
MH  - Sirtuins/*metabolism
PMC - PMC4746611
EDAT- 2016/01/16 06:00
MHDA- 2016/10/27 06:00
PMCR- 2016/02/01
CRDT- 2016/01/16 06:00
PHST- 2015/07/09 00:00 [received]
PHST- 2015/10/15 00:00 [revised]
PHST- 2015/11/23 00:00 [accepted]
PHST- 2016/01/16 06:00 [entrez]
PHST- 2016/01/16 06:00 [pubmed]
PHST- 2016/10/27 06:00 [medline]
PHST- 2016/02/01 00:00 [pmc-release]
AID - cr20164 [pii]
AID - 10.1038/cr.2016.4 [doi]
PST - ppublish
SO  - Cell Res. 2016 Feb;26(2):190-205. doi: 10.1038/cr.2016.4. Epub 2016 Jan 15.