The Drosophila BCL6 homolog ken and barbie promotes somatic stem cell self-renewal in the testis niche

摘要

Stemcellssustaintissueregenerationbytheirremarkableabilitytoreplenishthestemcellpoolandtogeneratedifferentiatingprogeny.Signalsfromlocalmicroenvironments,orniches,controlstemcellbehavior.IntheemDrosophila/emtestis,agroupofsomaticsupportcellscalledthehubcreatesastemcellnichebylocallyactivatingtheJanusKinase-SignalTransducerandActivatorofTranscription(JAK-STAT)pathwayintwoadjacenttypesofstemcells:germlinestemcells(GSCs)andsomaticcyststemcells(CySCs).Here,wefindthatemkenandbarbie/em(emken/em)isautonomouslyrequiredfortheself-renewalofCySCsbutnotGSCs.Furthermore,KenmisexpressionintheCySClineageinducesthecell-autonomousself-renewalofsomaticcellsaswellasthenonautonomousself-renewalofgermcellsoutsidetheniche.Thus,Ken,likeStat92Eanditstargetsspanid=""class="interref"data-locatorType="pdb"data-locatorKey="ZFH1"ZFH1/a/span(spanid="bbib38"ahref="#bib38"id="ancbbib38"class="intra_ref"LeathermanandDinardo,2008/a/span)andChinmo(spanid="bbib23"ahref="#bib23"id="ancbbib23"class="intra_ref"Flahertyetal.,2010/a/span),isnecessaryandsufficientforCySCrenewal.However,emken/emisnotaJAK-STATtargetinthetestis,butinsteadactsinparalleltoStat92EtoensureCySCself-renewal.KenrepressesasubsetofStat92Etargetsintheembryo(spanid="bbib3"ahref="#bib3"id="ancbbib3"class="intra_ref"Arbouzovaetal.,2006/a/span)suggestingthatKenmaintainsCySCsbyrepressingdifferentiationfactors.Insupportofthishypothesis,wefindthattheglobalJAK-STATinhibitoremProteintyrosinephosphatase61F/em(emPtp61F/em)isaJAK-STATtargetinthetestisthatisrepressedbyKen.Together,ourworkdemonstratesthatKenhasanimportantroleintheinhibitionofCySCdifferentiation.Studiesofemken/emmayinformourunderstandingofitsvertebrateorthologueemB-CellLymphoma6/em(spanid=""class="interref"data-locatorType="pdb"data-locatorKey="BCL6"emBCL6/em/a/span)andhowmisregulationofthisoncogeneleadstohumanlymphomas./p/div