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日期: 2004-05-12 今日/总浏览: 1/559
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Skeletalmusclehasaremarkablecapacitytoregeneratefollowingexerciseorinjuryandharborstwodifferenttypesofadultstemcellstoaccomplishthejob:satellitecellsandadultstemcellsthatcanbeisolatedassidepopulation(SP)cells.Acertaingroupofthesestemcellsisinvolvedinmuscletissuerepair,butisonlytriggeredintothemusclecelldevelopmentpathwaybyinjury.Thequestionthenarises:whatmolecularfactorsturntheseadultstemcellsintomusclecells?NowMichaelRudnickiandcolleagueshaveshownthatonegene,Pax7,hasacrucialroleinthisprocess.
1 _+ v, w ^7 H/ H9 X5 yInpreviousstudies,Rudnicki’sgroupdemonstratedthatPax7isrequiredtoturnadultstemcellsintomusclecellsduringregeneration.Here,theresearchersworkedwithmousemodelsandinvitroexperimentstoinvestigatewhetherPax7issufficienttoinitiatemusclecellformationininjuredtissue.
9 l* ]2 A3 s6 I( [5 wTheyshowthatstemcellstakenfromregeneratingmuscleinmicelackingthePax7genecouldnotbecomemusclecells,andthatbyputtingPax7backintostemcellstakenfromuninjuredmuscle,theycangenerateapopulationofcellsthatreadilydifferentiateintomusclecells.WhenstemcellsengineeredtoexpressPax7proteinswereinjectedintothemusclesofmicelackingdystrophin(theproteindefectiveinmusculardystrophy),thecellsdifferentiated,formingdystrophin-expressingmusclecellsinthedefectivemuscle.Thisshowsthatengineereddonorcellscandifferentiateinlivingtissueandhelprepairdamagedmuscleofrecipientmice.WhentheresearchersinjectedPax7(usingagenetherapyvirus)intothedamagedmuscleofmicelackingPax7,theyobservedtheproductionofmuscle-formingcellsthatnotonlygaverisetodifferentiatedmusclecells,butalsoaidedintissuerepair.
, s6 ]+ Y7 _2 {) \% d, i$ e. iTheresearchersarguethattheseresultsunequivocallyestablishPax7asakeyregulatorofmusclecelldifferentiationinspecificpopulationsofadultstemcellsduringmuscletissueregenerationinmice.IftherapeuticstrategiesthatactivatePax7inadultstemcellscanturnthemintomusclecells,effectivelyreplenishinginjuredordiseasedmuscletissue,there’shopeofreversingthedebilitatingeffectsofprogressivemuscle-wastingdiseases.Thoughtheusefulnessofsuchanapproachinhumanswillrequireintensiveinvestigation,theresultsonthesemouseadultstemcellsareencouraging.* M- c2 z8 O/ V$ S, v/ x, y2 E5 J
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Citation:SealeP,IshibashiJ,ScimA,RudnickiMA(2004)Pax7isnecessaryandsufficientforthemyogenicspecificationofCD45 :Sca1 stemcellsfrominjuredmuscle.PLoSBiol2(5):e130DOI:10.1371/journal.pbio.0020130
; j- P D' o4 R' J Moreinformation: http://www.plosbiology.org/plosonline/?request=get-document&doi=10.1371/journal.pbio.0020130
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发布者: 刘斌 |
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