RNA-Seq Analysis Reveals Different Dynamics of Differentiation of Human Dermis- and Adipose-Derived Stromal Stem Cells 英文参考文献.docVIP

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RNA-Seq Analysis Reveals Different Dynamics of Differentiation of Human Dermis- and Adipose-Derived Stromal Stem Cells 英文参考文献.doc

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RNA-Seq Analysis Reveals Different Dynamics of Differentiation of Human Dermis- and Adipose-Derived Stromal Stem Cells 英文参考文献

RNA-SeqAnalysisRevealsDifferentDynamicsof DifferentiationofHumanDermis-andAdipose-Derived StromalStemCells KerstiJa¨a¨ger1,2*,SaifulIslam3,PawelZajac3,StenLinnarsson3,ToomasNeuman1,4 1InstituteofGeneTechnology,TallinnUniversityofTechnology,Tallinn,Estonia,2CellinTechnologiesLLC,Tallinn,Estonia,3DepartmentofMedicalBiochemistryand Biophysics,KarolinskaInstitutet,Stockholm,Sweden,4ProtobiosLLC,Tallinn,Estonia Abstract Background:Tissueregenerationandrecoveryintheadultbodydependsonself-renewalanddifferentiationofstemand progenitor cells. Mesenchymal stem cells (MSCs) that have the ability to differentiate into various cell types, have been isolated from the stromal fraction of virtually all tissues. However, little is known about the true identity of MSCs. MSC populationsexhibitgreattissue-,location-andpatient-specificvariationingeneexpressionandareheterogeneousincell composition. Methodology/PrincipalFindings:Ouraimwastoanalyzethedynamicsofdifferentiationoftwocloselyrelatedstromalcell types,adiposetissue-derivedMSCs(AdMSCs)anddermalfibroblasts(FBs)alongadipogenic,osteogenicandchondrogenic lineagesusingmultiplexRNA-seqtechnology.Wefoundthatundifferentiateddonor-matchedAdMSCsandFBsaredistinct populationsthatstaydifferentupondifferentiationintoadipocytes,osteoblastsandchondrocytes.Thechangesinlineage- specificgeneexpressionoccurearlyindifferentiationandpersistovertimeinbothAdMSCsandFBs.Further,AdMSCsand FBs exhibit similar dynamics of adipogenic and osteogenic differentiation but different dynamics of chondrogenic differentiation. Conclusions/Significance:OurfindingssuggestthatstromalstemcellsincludingAdMSCsanddermalFBsexploitdifferent molecularmechanismsofdifferentiationtoreachacommoncellfate.Theearlymechanismsofdifferentiationarelineage- specific and are similar for adipogenic and osteogenic differentiation but are distinct for chondrogenic differentiation betweenAdMSCsandFBs. Citation: Ja¨a¨ger K, Islam S, Zajac P, Linnarsson S, Neuman T (2012) RNA-Seq Analysis Reveals