SUMOylation promotes survival and integration of neural stem cell grafts in ischemic stroke.
Peruzzotti Jametti, Luca
Johnson, Kory R
Van Den Bosch, Aletta
Hallenbeck, John M
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Bernstock, J., Peruzzotti Jametti, L., Leonardi, T., Vicario, N., Ye, D., Lee, Y., Maric, D., et al. (2019). SUMOylation promotes survival and integration of neural stem cell grafts in ischemic stroke.. EBioMedicine, 42 214-224. https://doi.org/10.1016/j.ebiom.2019.03.035
Background: Neural stem cell (NSC)-based therapies hold great promise for treating diseases of the central nervous system (CNS). However, several fundamental problems still need to be overcome to fully exploit the clinical potential of NSC therapeutics. Chief among them is the limited survival of NSC grafts within hostile microenvironments. Methods: Herein, we sought to engineer NSCs in an effort to increase graft survival within ischemic brain lesions via upregulation of global SUMOylation, a post-translational modification critically involved in mediating tolerance to ischemia/reperfusion. Findings: NSCs overexpressing the SUMO E2-conjugase Ubc9 displayed resistance to oxygen-glucose-deprivation/restoration of oxygen/glucose (OGD/ROG) and enhanced neuronal differentiation in vitro, as well as increased survival and neuronal differentiation when transplanted in mice with transient middle cerebral artery occlusion in vivo. Interpretation: Our work highlights a critical role for SUMOylation in NSC biology and identifies a biological pathway that can be targeted to increase the effectiveness of exogenous stem cell medicines in ischemic stroke. Fund: Intramural Research Program of the NINDS/NIH, the Italian Multiple Sclerosis Foundation (FISM), the Bascule Charitable Trust, NIH-IRTA-OxCam and Wellcome Trust Research Training Fellowships.
Neurons, Animals, Mice, Transgenic, Mice, Oxygen, Ubiquitin-Conjugating Enzymes, Glucose, Stem Cell Transplantation, Gene Expression Profiling, Computational Biology, Signal Transduction, Cell Cycle, Cell Survival, Gene Expression, Energy Metabolism, Male, Stroke, Neurogenesis, Sumoylation, Neural Stem Cells, Biomarkers
Intramural Research Program of the NINDS/NIH The Italian Multiple Sclerosis Foundation (FISM) The Bascule Charitable Trust NIH-IRTA-OxCam Wellcome Trust Research Training Fellowships
Bascule Charitable Trust (RG75149)
Wellcome Trust (105795/Z/14/Z)
WELLCOME TRUST (105795/Z/14/Z)
Embargo Lift Date
External DOI: https://doi.org/10.1016/j.ebiom.2019.03.035
This record's URL: https://www.repository.cam.ac.uk/handle/1810/290829