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日期: 2004-05-12 今日/总浏览: 1/559& z+ [) ^2 g! D2 v1 [, O( c
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: }1 N% L" f" [$ ]( c" uSkeletalmusclehasaremarkablecapacitytoregeneratefollowingexerciseorinjuryandharborstwodifferenttypesofadultstemcellstoaccomplishthejob:satellitecellsandadultstemcellsthatcanbeisolatedassidepopulation(SP)cells.Acertaingroupofthesestemcellsisinvolvedinmuscletissuerepair,butisonlytriggeredintothemusclecelldevelopmentpathwaybyinjury.Thequestionthenarises:whatmolecularfactorsturntheseadultstemcellsintomusclecells?NowMichaelRudnickiandcolleagueshaveshownthatonegene,Pax7,hasacrucialroleinthisprocess.
6 Z- E# f6 I7 M4 Y' Z8 Y4 r" X F, uInpreviousstudies,Rudnicki’sgroupdemonstratedthatPax7isrequiredtoturnadultstemcellsintomusclecellsduringregeneration.Here,theresearchersworkedwithmousemodelsandinvitroexperimentstoinvestigatewhetherPax7issufficienttoinitiatemusclecellformationininjuredtissue.
7 w0 G+ B1 S, z( n/ w% m1 F8 JTheyshowthatstemcellstakenfromregeneratingmuscleinmicelackingthePax7genecouldnotbecomemusclecells,andthatbyputtingPax7backintostemcellstakenfromuninjuredmuscle,theycangenerateapopulationofcellsthatreadilydifferentiateintomusclecells.WhenstemcellsengineeredtoexpressPax7proteinswereinjectedintothemusclesofmicelackingdystrophin(theproteindefectiveinmusculardystrophy),thecellsdifferentiated,formingdystrophin-expressingmusclecellsinthedefectivemuscle.Thisshowsthatengineereddonorcellscandifferentiateinlivingtissueandhelprepairdamagedmuscleofrecipientmice.WhentheresearchersinjectedPax7(usingagenetherapyvirus)intothedamagedmuscleofmicelackingPax7,theyobservedtheproductionofmuscle-formingcellsthatnotonlygaverisetodifferentiatedmusclecells,butalsoaidedintissuerepair.+ R2 S; |4 ]$ C! _$ y }1 g6 o
TheresearchersarguethattheseresultsunequivocallyestablishPax7asakeyregulatorofmusclecelldifferentiationinspecificpopulationsofadultstemcellsduringmuscletissueregenerationinmice.IftherapeuticstrategiesthatactivatePax7inadultstemcellscanturnthemintomusclecells,effectivelyreplenishinginjuredordiseasedmuscletissue,there’shopeofreversingthedebilitatingeffectsofprogressivemuscle-wastingdiseases.Thoughtheusefulnessofsuchanapproachinhumanswillrequireintensiveinvestigation,theresultsonthesemouseadultstemcellsareencouraging.- b- P, n& f5 ~; q1 z
# j: {. n! ~( \5 M) C9 T: @6 wCitation:SealeP,IshibashiJ,ScimA,RudnickiMA(2004)Pax7isnecessaryandsufficientforthemyogenicspecificationofCD45 :Sca1 stemcellsfrominjuredmuscle.PLoSBiol2(5):e130DOI:10.1371/journal.pbio.00201306 D! l" q' |3 m, i; o, {
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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