title: Genetic modification of H2AX renders mesenchymal stromal cell-derived dopamine neurons more resistant to DNA damage and subsequent apoptosis.
abstract: Aberrant production of reactive oxygen species (ROS) and its impact on the integrity of genomic DNA have been considered one of the major risk factors for the loss of dopaminergic neurons in Parkinson's disease (PD). Stem cell transplantation as a strategy to replenish new functional neurons has great potential for PD treatment. However, limited survival of stem cells post-transplantation has always been an obstacle ascribed to the existence of neurotoxic environment in PD patients.
  
  
  
  To improve the survival of transplanted stem cells for PD treatment, we explored a new strategy based on the function of the H2AX gene (H2A histone family, member X) in determination of DNA repair and cell apoptosis. We introduced a mutant form Y142F of H2AX into dopamine (DA) neuron-like cells differentiated from bone marrow-derived mesenchymal stromal cells (BMSCs).
  
  
  
  Expression of H2AX(Y142F) renders DA neuron-like cells more resistant to DNA damage and subsequent cell death induced by ultraviolet irradiation and 1-methyl-4-phenylpyridinium (MPP+) treatment.
  
  
  
  This is a meaningful attempt to improve the sustainability of BMSC-derived dopamine neurons under a brain neurotoxic environment. Further studies are needed to evaluate the implications of our findings in stem cell therapy for PD and related diseases.
authors.affiliation: Department of Neuroscience, Mayo Clinic Florida, Jacksonville, Florida, USA. Electronic address: jiang.peizhou@mayo.edu.
authors.forename: Peizhou
authors.initials: P
authors.lastname: Jiang
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic Florida, Jacksonville, Florida, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Neuroscience, Mayo Clinic Florida, Jacksonville, Florida, USA.
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Yen
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic Florida, Jacksonville, Florida, USA.
authors.forename: Abba C
authors.initials: AC
authors.lastname: Zubair
authors.affiliation: Department of Neuroscience, Mayo Clinic Florida, Jacksonville, Florida, USA. Electronic address: dickson.dennis@mayo.edu.
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001854:Bone Marrow Cells / Q000166:cytology; D001921:Brain / Q000378:metabolism; D016923:Cell Death; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D004249:DNA Damage / Q000235:genetics*; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000166:cytology / Q000378:metabolism*; D006657:Histones / Q000235:genetics*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009474:Neurons / Q000166:cytology; D010300:Parkinson Disease / Q000473:pathology / Q000628:therapy*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C468783:H2AX protein, human; D006657:Histones; D017382:Reactive Oxygen Species; D004298:Dopamine
keywords: DNA damage; H2AX; Parkinson's disease; lentivirus infection; mesenchymal stromal cells