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日期: 2004-05-12 今日/总浏览: 1/559; E& a3 H) M9 g& i, O
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( W: j) U* k, ~+ KSkeletalmusclehasaremarkablecapacitytoregeneratefollowingexerciseorinjuryandharborstwodifferenttypesofadultstemcellstoaccomplishthejob:satellitecellsandadultstemcellsthatcanbeisolatedassidepopulation(SP)cells.Acertaingroupofthesestemcellsisinvolvedinmuscletissuerepair,butisonlytriggeredintothemusclecelldevelopmentpathwaybyinjury.Thequestionthenarises:whatmolecularfactorsturntheseadultstemcellsintomusclecells?NowMichaelRudnickiandcolleagueshaveshownthatonegene,Pax7,hasacrucialroleinthisprocess.6 B8 D/ W# m/ g2 x8 r- _4 S
Inpreviousstudies,Rudnicki’sgroupdemonstratedthatPax7isrequiredtoturnadultstemcellsintomusclecellsduringregeneration.Here,theresearchersworkedwithmousemodelsandinvitroexperimentstoinvestigatewhetherPax7issufficienttoinitiatemusclecellformationininjuredtissue./ x/ v1 a1 ]& n" _- E
TheyshowthatstemcellstakenfromregeneratingmuscleinmicelackingthePax7genecouldnotbecomemusclecells,andthatbyputtingPax7backintostemcellstakenfromuninjuredmuscle,theycangenerateapopulationofcellsthatreadilydifferentiateintomusclecells.WhenstemcellsengineeredtoexpressPax7proteinswereinjectedintothemusclesofmicelackingdystrophin(theproteindefectiveinmusculardystrophy),thecellsdifferentiated,formingdystrophin-expressingmusclecellsinthedefectivemuscle.Thisshowsthatengineereddonorcellscandifferentiateinlivingtissueandhelprepairdamagedmuscleofrecipientmice.WhentheresearchersinjectedPax7(usingagenetherapyvirus)intothedamagedmuscleofmicelackingPax7,theyobservedtheproductionofmuscle-formingcellsthatnotonlygaverisetodifferentiatedmusclecells,butalsoaidedintissuerepair.
H$ _9 w4 R( ~8 I' fTheresearchersarguethattheseresultsunequivocallyestablishPax7asakeyregulatorofmusclecelldifferentiationinspecificpopulationsofadultstemcellsduringmuscletissueregenerationinmice.IftherapeuticstrategiesthatactivatePax7inadultstemcellscanturnthemintomusclecells,effectivelyreplenishinginjuredordiseasedmuscletissue,there’shopeofreversingthedebilitatingeffectsofprogressivemuscle-wastingdiseases.Thoughtheusefulnessofsuchanapproachinhumanswillrequireintensiveinvestigation,theresultsonthesemouseadultstemcellsareencouraging.4 s, D' h% a2 X2 I" f' k
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Citation:SealeP,IshibashiJ,ScimA,RudnickiMA(2004)Pax7isnecessaryandsufficientforthemyogenicspecificationofCD45 :Sca1 stemcellsfrominjuredmuscle.PLoSBiol2(5):e130DOI:10.1371/journal.pbio.0020130
0 e8 m1 x% B3 T Moreinformation: http://www.plosbiology.org/plosonline/?request=get-document&doi=10.1371/journal.pbio.00201304 S+ A" d& u2 R: W
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发布者: 刘斌 |
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