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日期: 2004-05-12 今日/总浏览: 1/559; B# _! H; M$ B Z$ b: S2 Y
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Skeletalmusclehasaremarkablecapacitytoregeneratefollowingexerciseorinjuryandharborstwodifferenttypesofadultstemcellstoaccomplishthejob:satellitecellsandadultstemcellsthatcanbeisolatedassidepopulation(SP)cells.Acertaingroupofthesestemcellsisinvolvedinmuscletissuerepair,butisonlytriggeredintothemusclecelldevelopmentpathwaybyinjury.Thequestionthenarises:whatmolecularfactorsturntheseadultstemcellsintomusclecells?NowMichaelRudnickiandcolleagueshaveshownthatonegene,Pax7,hasacrucialroleinthisprocess.
3 s9 o, D" |9 M. I6 @# L4 q0 u# ~ UInpreviousstudies,Rudnicki’sgroupdemonstratedthatPax7isrequiredtoturnadultstemcellsintomusclecellsduringregeneration.Here,theresearchersworkedwithmousemodelsandinvitroexperimentstoinvestigatewhetherPax7issufficienttoinitiatemusclecellformationininjuredtissue.
% i" L' q1 Z) u2 u1 z7 lTheyshowthatstemcellstakenfromregeneratingmuscleinmicelackingthePax7genecouldnotbecomemusclecells,andthatbyputtingPax7backintostemcellstakenfromuninjuredmuscle,theycangenerateapopulationofcellsthatreadilydifferentiateintomusclecells.WhenstemcellsengineeredtoexpressPax7proteinswereinjectedintothemusclesofmicelackingdystrophin(theproteindefectiveinmusculardystrophy),thecellsdifferentiated,formingdystrophin-expressingmusclecellsinthedefectivemuscle.Thisshowsthatengineereddonorcellscandifferentiateinlivingtissueandhelprepairdamagedmuscleofrecipientmice.WhentheresearchersinjectedPax7(usingagenetherapyvirus)intothedamagedmuscleofmicelackingPax7,theyobservedtheproductionofmuscle-formingcellsthatnotonlygaverisetodifferentiatedmusclecells,butalsoaidedintissuerepair.. r7 @$ ]: I" d/ X2 d, H- V
TheresearchersarguethattheseresultsunequivocallyestablishPax7asakeyregulatorofmusclecelldifferentiationinspecificpopulationsofadultstemcellsduringmuscletissueregenerationinmice.IftherapeuticstrategiesthatactivatePax7inadultstemcellscanturnthemintomusclecells,effectivelyreplenishinginjuredordiseasedmuscletissue,there’shopeofreversingthedebilitatingeffectsofprogressivemuscle-wastingdiseases.Thoughtheusefulnessofsuchanapproachinhumanswillrequireintensiveinvestigation,theresultsonthesemouseadultstemcellsareencouraging.
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3 |# p( c* H/ I* p4 j, Q9 U4 {Citation:SealeP,IshibashiJ,ScimA,RudnickiMA(2004)Pax7isnecessaryandsufficientforthemyogenicspecificationofCD45 :Sca1 stemcellsfrominjuredmuscle.PLoSBiol2(5):e130DOI:10.1371/journal.pbio.00201306 o7 U1 O* P2 R" M6 p7 p
Moreinformation: http://www.plosbiology.org/plosonline/?request=get-document&doi=10.1371/journal.pbio.00201300 d& ^5 v# w$ T: w
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发布者: 刘斌 |
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