plasticity in the lung making and breaking cell identity purushothama rao tata资料.pdf

该【plasticity in the lung making and breaking cell identity purushothama rao tata资料 】是由【彩屏】上传分享，文档一共【12】页，该文档可以免费在线阅读，需要了解更多关于【plasticity in the lung making and breaking cell identity purushothama rao tata资料 】的内容，可以使用淘豆网的站内搜索功能，选择自己适合的文档，以下文字是截取该文章内的部分文字，如需要获得完整电子版，请下载此文档到您的设备，方便您编辑和打印。:..?|Development(2017)144,755-766doi::makingandbreakingcellidentityPurushothamaRaoTata1,2,3,*andJayarajRajagopal1,2,3,4,5,?ABSTRACTthebehaviorofhumanlungcelllineageswillrequiretheapplicationIncontrasttoaprioremphasisonthefinalityofcellfatedecisionsinofnewtechniques,suchasmitochondrialmutationtracingordevelopmentalsystems,putationalsinglecelllineagereconstruction(Teixeiraetal.,;al.,2014).lung,,,maintainastableidentityduringsteadystateenvironment,secretion,regeneration,repellinginfection,conditions,,whereasdifferentcelllineagesoftheadultmammalianlungandtheirciliatedcellsusetheirciliatopropeldebrisoutofthelung(,whichisconstantlyexposedtoandLi,1997).Moreproximalregionsofthemurineairwayinfectionandaerosolizedtoxins,epithelialplasticitymightbemoreofepitheliumpossessbasalcells,whichactasepithelialstem/arulethananexception,,municatewiththeimmunesystemandtheKEYWORDS:Cellularheterogeneity,Cellularplasticity,,ontheotherhand,tracing,Lunginjuryrepair,Lungregeneration,Lungstemcellscontainsthintype1cellsthatpermitgasexchange,,thesemajorepithelialcellcompartments:theairways,whichfunctiontoconductgases,,lessfrequentcelltypes,suchasMcellsandbrushcompriseasmanyas40differentcelltypes(Franksetal.,2008),cellsarealreadyknowntoexist,(Branchfieldetal.,2016;arisesintheembryonicforegut;an’sepitheliumissourcedKrastevaetal.,2012;Reidetal.,2005;Songetal.,2012;fromtheendoderm,whereasthemesenchymeisofmesodermalTeitelbaumetal.,1999).,suchassecretorycellsortype2cells,subsetsofcellsaremurinelungbecauseitistheepithelialcelllineagesthathavebeenthoughttopossessdifferingprogenitorcellactivitiesevenunderthemostwell,albeitpreliminarily,,thesteadystateconditions(Barkauskasetal.,2013;Guhaetal.,2014;epithelialresponsestoinjuryhavebeenmorecloselyscrutinizedReynoldsetal.,2002)andmuchmoreislikelytobelearnedaboutpartmentsofthelung,,-tracingstudiesdescribedhereinmaypossessesquiescentstem/,butitisalsoenormousreparativepotential,,-tracing(HerrigesandMorrisey,2014;al.,2014;,suggestionsconcerningtheMorrisey,2014).InthisReview,wediscussourcurrentandpleteunderstandingofthediversityofepithelialstemandanismorprogenitorcellsinthelung,,weusethetermenvironmentsareknowntoelicitcellplasticity,,MassachusettsGeneralHospital,185Forexample,amature‘terminallydifferentiated’cellmightde-CambridgeStreet,Boston,MA02114,,,oneCambridge,MA02138,,DivisionofPulmonaryandCriticalCareMedicine,MassachusettsGeneralHospital,Boston,differentiatedmaturecellmighttransdifferentiateintoanotherMA02114,,,Boston,MA02114,,MassachusettsEyeandEar,Boston,MA02114,,suchasmaturationstateandneighboringcell-to-cell*Presentaddress:DepartmentofCellBiology,DukeUniversityMedicalSchool,Durham,NC27710,,themajorityofthefindings?(******@)Wherepossible,.,0000-0003-4837-0337;.,0000-0003-3190-,however,savepointingDEVELOPMENT755:..REVIEWDevelopment(2017)144,755-766doi:,ourinadditiontosecretoryandciliatedcells,,(al.,2015).CellulardiversityandlineageinthemammalianlungDifferentinjurymodels,includingthosethatemploygaseousThedevelopmentaloriginofthelungepitheliumtoxinssuchassulphurdioxideandchlorine,aswellasthosethatInmammals,thelungepitheliumoriginatesfromtheanterioremployinfectiousagentssuchasinfluenza,havebeenusedtostudyendoderm,anstheregenerationofpseudostratifiedairwayepithelium(Matalonandincludingtheesophagus,thyroid,pancreas,liverandintestineMaull,2010;O’al.,2013).Itisinterestingtonotethatthe(CardosoandLü,2006;HerrigesandMorrisey,2014;icsofcellproliferationanddifferentiationarealmostidenticalHogan,2004;Wells,2015).,monpatternedalongthenewlyformingproximodistalaxisoftheintermediatecellthatco-expressesbasal(KRT5)andluminalan,inaprocessreferredtoasbranchingmorphogenesis(KRT8)(Alanisetal.,2014;Queetal.,2009).Initially,thetracheaandciliatedandsecretorycells(Morietal.,2015;Rocketal.,2011a).larynxderivefromadistinctregionoftheguttubeknownastheRecentstudieshavealsodemonstratedthat,understeadystatelaryngotrachealgroove,whereastherestofthelungderivesfromconditions,,asmallpopulationofbasalcellsexpressesthelaryngotrachealgroove(Queetal.,2006,2007).TheembryonicdifferentiationmarkerKRT8(al.,2015).Similarly,distallungbudor‘tip’(Notch2ICD)orc-myb(Myb),earlydifferentiationmarkersepithelialtipsalsodivideiterativelyandsequentiallytolayouttheforsecretoryandciliatedcells,respectively(Pardo-Sagantaetal.,primarybronchialairways,thenthesecondarybronchi,andsoon2015a).,thedistaltipheterogeneous,urina‘primed’,,althoughpriorworkhassuggestedthatparticularTheadultlungpossessesasinglelargeairwayknownasthetrachea,subpopulationsofbasalcellshavemorelimitedpotential,,whichisepithelialcellsinvitro(Ghoshetal.,2011;Tataetal.,2013).,,thenumberofbasalcellsexpressingepitheliumis,inturn,surroundedandprotectedbydenseconnectivec-mybandNotch2ICDincreasesimmediatelyfollowinginjury,tissueanddiscontinuousc-shapedcartilageringsthataresealedbysuggestingthatinjury-,thesegregationof‘primed’basalcellsubpopulations,orthatthelosspseudostratifiedepitheliumextendstothefirstandlargestdivisionofsuppressivesignalsunleashesanintrinsictendencytowardsoftheairwayknownasthebronchi().Here,mitted’basalcells(Pardo-Sagantaconsistsofbasalcellslocateddirectlyatopthebasementmembrane,etal.,2015a).luminalsecretoryandciliatedcells,andasmatteringofpulmonaryThemechanismsthatregulateinjury-inducedsegregationremainneuroendocrinecells(PNECs)(RockandHogan,2011;Rocketal.,).amongstbasalcellsubpopulationsthatpredicttheirfuturebehavior,ashasbeenshowninothersystemssuchastheintestine(Kimetal.,Basalcells2014).IthasbeenrecentlysuggestedthatdynamicreactiveoxygenBasalcellsaremorphologicallycharacterizedbytheirsmallheightspecieslevelsinbasalcellscanregulatetheirsymmetricversusrelativetoadjacentluminalcells,elldivision(Pauletal.,2014).Itwouldbeinterestingthebasementmembrane(;)(EvansandPlopper,toassesswhetherandhowreactiveoxygenspecieslevelsregulate1988).Atthemolecularlevel,basalcellsarecharacterizedbytheinjury-associatedbasalcellheterogeneity(Pauletal.,2014).expressionoftheN-terminus-truncatedisoformofTRP63(hereafterInmice,basalcells,atthepopulationlevel,areprimarilypresentreferredtoasp63),cytokeratin5(KRT5),nervegrowthfactorinthetracheaandmainstembronchi(al.,2014;Rockandreceptor(NGFR)andpodoplanin(PDPN)(al.,2014;RockHogan,2011;Rocketal.,2009).However,inhumans,basalcellsetal.,2009).Earlystudiesusingxenograftsofpurifiedbasalcellsextenddistallyintothesmallbronchioles().Whethertherearesuggestedthatthesecellscouldself-renewandweremultipotent,molecularorfunctionaldifferencesinthebasalcellsofthetracheameaningthattheycouldgeneratenotonlymorebasalcells,,secretoryandciliatedcells(Liuetal.,1994;Rocketal.,2010).Morethemurinesmallairway,whichlackssignificantnumbersofbasalrecently,anoidcells,urred,culturesandair-liquidinterface(ALI)cultures(Rocketal.,2009;histologicallymirrorsonlyasmallfractionofthemostdistalhumanTataetal.,2013).Furthermore,theidentificationofclonesofairwayairway().Basedlargelyonthepresenceofbasalcells,theracheahasbeenpositedasabettermodelforthestudyofhumanshasprovidedsomeinitialevidencethathumanbasalcellshumanairwaysdisease(al.,2014);however,itremainsaresimilarlymultipotentinvivo(Teixeiraetal.,2013).Theabilityunclearhowhumanairwaycelldiversitycorrespondstoitsmurineofbasalcellstorestorenormalnumbersofrelativelyrarecelltypes,,differentregionsofthemouseairwaymayDEVELOPMENT756:..REVIEWDevelopment(2017)144,755-766doi: