The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
SIRT6 safeguards human mesenchymal stem cells from oxidative stress by coactivating NRF2
Open accessAbstract
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.
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Self-citationA Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging
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Cited by
NRF2, a Transcription Factor for Stress Response and Beyond
He, F., Ru, X., & Wen, T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21134777 · Cited by 1,820
Cellular Senescence as a Mechanism and Target in Chronic Lung Diseases
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Repression of the Antioxidant NRF2 Pathway in Premature Aging
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Self-citationRedox control of senescence and age-related disease.
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Metadata
- Authors
- Pan, H., Guan, D., Liu, X., Li, J., Wang, L., Wu, J., Zhou, J., Zhang, W., Ren, R., Zhang, W., Li, Y., Yang, J., Hao, Y., Yuan, T., Yuan, G., Wang, H., Ju, Z., Mao, Z., Li, J., Qu, J., Tang, F., & Liu, G.-H.
- Venue
- Cell Research
- Published
- 2016-01-15
- Volume
- 26
- Issue
- 2
- Pages
- 190-205
- ISSN
- 1001-0602 (ISSN-L)
- 1748-7838
- OpenAlex
- W2302321360
- Cited by
- 335
- References
- 15
- FWCI
- 16.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Pan, H., Guan, D., Liu, X., Li, J., Wang, L., Wu, J., Zhou, J., Zhang, W., Ren, R., Zhang, W., Li, Y., Yang, J., Hao, Y., Yuan, T., Yuan, G., Wang, H., Ju, Z., Mao, Z., Li, J., . . . Liu, G.-H. (2016). SIRT6 safeguards human mesenchymal stem cells from oxidative stress by coactivating NRF2. Cell Research. https://doi.org/10.1038/cr.2016.4
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