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日期: 2002-12-02 今日/总浏览: 1/696* l( K6 v5 ~. Z( |/ z p6 _
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Ronald D.G. McKay, Ph.D.
& \ Q T% K0 J e6 p- g' vScientistshaveidentifiedacritical,newstemcellprotein?amarkedadvanceintheelucidationofthemolecularblueprintofstemcells.
" _. s! I4 P) y5 X7 b8 |' TDrs.RobertTsaiandRonaldMcKayattheNIHhavediscoveredanovelgene,callednucleostemin,whoseencodedproteinisnecessaryformaintainingtheproliferativecapacityofembryonicandadultstemcells,andpossiblysometypesofcancercells.TheirreportispublishedintheDecember1issueofthescientificjournalGenes&Development.
& `5 [* Y% v* p) `7 mEmbryonicstemcellsarepluripotentprogenitorcellsthatcandifferentiateintoallofthecelltypesofthebody.Adultstemcells,incontrast,havealessversatilepotential:Theirdifferentiationisgenerallyrestrictedtothecelltypesofaspecifictissue(althoughrecentworkhasexpandedthepreviouslyknownrangeofadultstemcelldifferentiationpotential).% ^, m8 l) W6 ?' D) h8 p
Akeyfeatureofbothembryonicandadultstemcellsistheircapacityforself-renewalaswellasdifferentiation?ensuringthataconstantpoolofundifferentiatedstemcellsalwaysexists.Drs.TsaiandMcKayhaveidentifiednucleosteminasacriticalregulatorofthisdelicatebalance.
B' y& t$ Z/ s3 E. t- kDrs.TsaiandMcKayoriginallyidentifiednucleosteminasaproteinabundantlyexpressedinratCNS(centralnervoussystem)stemcellsthatismarkedlydown-regulatedduringdifferentiation,suggestingapossibleroleinstemcellmaintenance.Theresearcherswentontoshowthatnucleosteminisexpressedinvariousadultandembryonicstemcellpopulations,aswellasinsomehumancancercelllines,andthatitsexpressionisconsistentlyturned-offduringthedifferentiationofstemcellsintomorespecializedcelltypes.2 e7 }! H$ u! M. L4 V
UsingtheRNAigenesilencingmethod,Drs.TsaiandMcKaydisruptednormalnucleosteminexpressionpatternsinrodentCNSstemcellsandhumanosteosarcomacancercells.Theyfoundthattheaberrantdown-regulationofnucleostemininthesecellscausedadecreaseincellproliferation,suggestingthattheexpressionofnucleosteminisrequiredforstemcell--andsomecancercell--proliferation.+ o2 s5 P# L( r" ?6 j0 } j/ K5 W
Althoughtheprecisemechanismofnucleosteminactionisnotyetfullyunderstood,theidentificationofagenewhoseproteinproductspecificallypromotestheproliferationofstemcellsandsomecancercellshasimportantclinicalimplicationsforboththeuseofstemcellsinregenerativemedicineaswellasthetreatmentofcancer.AsDr.Tsaiexplains,Thecharacterizationofnucleosteminsuggeststhatauniqueprimitivestateissharedbybothstemcellsandcancercelllines.Theidentificationofcommonmoleculessharedbybothstemcellsandcancercellsmayfacilitatethediscoveryofself-renewingpopulationswithinagiventumorbyevaluatingtheirexpressionlevels.Perhaps,inthefuture,targetingthesecellswillachieveabettertherapeuticoutcome.
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5 a" S+ A! {3 O( b3 n* F8 i# [作者:
- z6 g: L. e" i& f9 q$ z4 J" O X来源: Cold Spring Harbor Laboratory
# t: b8 |: x$ b; V( z& b4 F发布者: 刘斌 |
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