DHP-Derivative and Low Oxygen Tension Effectively Induces Human Adipose Stromal Cell Reprogramming 英文参考文献.docVIP

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DHP-Derivative and Low Oxygen Tension Effectively Induces Human Adipose Stromal Cell Reprogramming 英文参考文献.doc

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DHP-Derivative and Low Oxygen Tension Effectively Induces Human Adipose Stromal Cell Reprogramming 英文参考文献

DHP-DerivativeandLowOxygenTensionEffectively InducesHumanAdiposeStromalCellReprogramming MinKiJee1,JiHoonKim2,YongManHan2,SungJunJung5,KyungSunKang3,DongWookKim4 ,Soo KyungKang1* 1DepartmentofBiotechnology,CollegeofVeterinaryMedicine,SeoulNationalUniversity,Seoul,Korea,2DepartmentofBiologicalSciences,KoreaAdvancedInstituteof ScienceandTechnology(KAIST),Daejeon,Korea,3DepartmentofVeterinaryPublicHealth,LaboratoryofStemCellandTumorBiology,CollegeofVeterinaryMedicine, Seoul National University, Seoul, Korea, 4Department of Physiology, College of Medicine, Yonsei University, Seoul, Korea, 5Department of Physiology, College of Medicine,HanYangUniversity,Seoul,Korea Abstract BackgroundandMethods:Inthisstudy,weutilizedacombinationoflowoxygentensionandanovelanti-oxidant,4-(3,4- dihydroxy-phenyl)-derivative (DHP-d) to directly induce adipose tissue stromal cells (ATSC) to de-differentiate into more primitivestemcells.De-differentiatedATSCswasoverexpressstemnessgenes,Rex-1,Oct-4,Sox-2,andNanog.Additionally, demethylationoftheregulatoryregionsofRex-1,stemnesses,andHIF1aandscavengingofreactiveoxygenspecieswere finallyresultedinanimprovedstemcellbehaviorofde-differentiateATSC(de-ATSC).ProliferationactivityofATSCsafter dedifferentiationwasinducedbyREX1,Oct4,andJAK/STAT3directlyorindirectly.De-ATSCsshowedincreasedmigration activitythatmediatedbyP38/JUNKandERKphosphorylation.Moreover,regenerativeefficacyofde-ATSCengraftedspinal cord-injuredratsandchemical-induceddiabetesanimalsweresignificantlyrestoredtheirfunctions. Conclusions/Significance:Ourstemcellremodelingsystemmayprovideagoodmodelwhichwouldprovideinsightinto themolecularmechanismsunderlyingATSCproliferationandtransdifferentiation.Also,thesemultipotentstemcellscanbe harvestedmayprovideuswithavaluablereservoirofprimitiveandautologousstemcellsforuseinabroadspectrumof regenerativecell-baseddiseasetherapy. Citation: JeeMK, Kim JH, HanYM,Jung SJ,Kang KS, et al.(2010) DHP-Derivative andLow Oxygen TensionEffectively Induces Human