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日期: 2002-12-02 今日/总浏览: 1/6966 {8 L, Y) Q$ o; x2 B0 P' v" F
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) N4 ?: @- _0 |( fRonald D.G. McKay, Ph.D.
5 L# m7 k, o0 Y+ Q uScientistshaveidentifiedacritical,newstemcellprotein?amarkedadvanceintheelucidationofthemolecularblueprintofstemcells.! k4 y" g" _4 Z' a5 E+ ^: n
Drs.RobertTsaiandRonaldMcKayattheNIHhavediscoveredanovelgene,callednucleostemin,whoseencodedproteinisnecessaryformaintainingtheproliferativecapacityofembryonicandadultstemcells,andpossiblysometypesofcancercells.TheirreportispublishedintheDecember1issueofthescientificjournalGenes&Development.
0 l1 Z) S8 N7 I, G! P# XEmbryonicstemcellsarepluripotentprogenitorcellsthatcandifferentiateintoallofthecelltypesofthebody.Adultstemcells,incontrast,havealessversatilepotential:Theirdifferentiationisgenerallyrestrictedtothecelltypesofaspecifictissue(althoughrecentworkhasexpandedthepreviouslyknownrangeofadultstemcelldifferentiationpotential).
; H( u5 y2 v, VAkeyfeatureofbothembryonicandadultstemcellsistheircapacityforself-renewalaswellasdifferentiation?ensuringthataconstantpoolofundifferentiatedstemcellsalwaysexists.Drs.TsaiandMcKayhaveidentifiednucleosteminasacriticalregulatorofthisdelicatebalance.
' U. a7 X5 s* S `, [Drs.TsaiandMcKayoriginallyidentifiednucleosteminasaproteinabundantlyexpressedinratCNS(centralnervoussystem)stemcellsthatismarkedlydown-regulatedduringdifferentiation,suggestingapossibleroleinstemcellmaintenance.Theresearcherswentontoshowthatnucleosteminisexpressedinvariousadultandembryonicstemcellpopulations,aswellasinsomehumancancercelllines,andthatitsexpressionisconsistentlyturned-offduringthedifferentiationofstemcellsintomorespecializedcelltypes./ h! Y0 }, m# t# P7 P
UsingtheRNAigenesilencingmethod,Drs.TsaiandMcKaydisruptednormalnucleosteminexpressionpatternsinrodentCNSstemcellsandhumanosteosarcomacancercells.Theyfoundthattheaberrantdown-regulationofnucleostemininthesecellscausedadecreaseincellproliferation,suggestingthattheexpressionofnucleosteminisrequiredforstemcell--andsomecancercell--proliferation., s' E, D9 m2 y! y! {
Althoughtheprecisemechanismofnucleosteminactionisnotyetfullyunderstood,theidentificationofagenewhoseproteinproductspecificallypromotestheproliferationofstemcellsandsomecancercellshasimportantclinicalimplicationsforboththeuseofstemcellsinregenerativemedicineaswellasthetreatmentofcancer.AsDr.Tsaiexplains,Thecharacterizationofnucleosteminsuggeststhatauniqueprimitivestateissharedbybothstemcellsandcancercelllines.Theidentificationofcommonmoleculessharedbybothstemcellsandcancercellsmayfacilitatethediscoveryofself-renewingpopulationswithinagiventumorbyevaluatingtheirexpressionlevels.Perhaps,inthefuture,targetingthesecellswillachieveabettertherapeuticoutcome.
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作者:
" z* M/ Q9 l7 w5 `来源: Cold Spring Harbor Laboratory
# M5 I6 `+ N$ @; [$ e) h发布者: 刘斌 |
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