Letterhttps://doi.org/10.1038/s41586-018-0190-3GLI1-expressingmesenchymalcellsformtheessentialWnt-secretingnicheforcolonstemcellsBaharDegirmenci1,4,tomasValenta1,2,4*,SlavicaDimitrieva3,GeorgeHausmann1&KonradBasler1*Wnt–β-cateninsignallingplaysapivotalroleinthehomeostasisoftheintestinalepitheliumbypromotingstemcellrenewal1,2.Inthesmallintestine,epithelialPanethcellssecreteWntligandsandthusadoptthefunctionofthestemcellnichetomaintainepithelialhomeostasis3,4.Itisunclearwhichcellscomprisethestemcellnicheinthecolon.HereweshowthatsubepithelialmesenchymalGLI1-expressingcellsformthisessentialniche.BlockingWntsecretionfromGLI1-expressingcellspreventscolonicstemcellrenewalinmice:thestemcellsarelostand,asaconsequence,theintegrityofthecolonicepitheliumiscorrupted,leadingtodeath.GLI1-expressingcellsalsoplayanimportantroleinthemaintenanceofthesmallintestine,wheretheyserveasareserveWntsourcethatbecomescriticalwhenWntsecretionfromepithelialcellsisprevented.OurdatasuggestamechanismbywhichthestemcellnicheisadjustedtomeettheneedsoftheintestineviaadaptivechangesinthenumberofmesenchymalGLI1-expressingcells.Intestinalepithelialstemcells(IEScells)serveasaparadigmforadultstemcells.Stem-cellpopulationsresideinniches—microenvironmentsthatregulatetheparticipationofstemcellsintissuegeneration,main-tenanceandrepair5,6.Wntligandsareacriticalcomponentprovidedbyintestinalstemcellniches.Inthesmallintestineepithelium,theprimarynichecomprisesterminallydifferentiatedPanethcells,whichactasasourceofWntsignallingmolecules3,7,8.InvitrostudieshaveshownthatWntspro-videdbyPanethcellsaresufficienttomaintainepithelialrenewal.Itwasthereforeunexpectedthathomeostasisofthesmallintestineepi-theliumtoleratesthelossofPanethcellsortheabsenceofepithelialWntsecretion1,9–11.Incontrasttothesituationinthesmallintestine,theidentityofthecellsthatconstitutetheWnt-producingnicheinthecolonhasremainedamystery.Unlikethesmallintestine,coloniccryptsdonotcontainPanethcellsoranyotherWnt-secretingepithelialcelltype7,8,12.Analy...
