ImmunityReviewNichesforHematopoieticStemCellsandTheirProgenyQiaozhiWei1,2andPaulS.Frenette1,2,3,*1RuthL.andDavidS.GottesmanInstituteforStemCellandRegenerativeMedicineResearch2DepartmentofCellBiology3DepartmentofMedicineAlbertEinsteinCollegeofMedicine,Bronx,NY10461,USA*Correspondence:paul.frenette@einstein.yu.eduhttps://doi.org/10.1016/j.immuni.2018.03.024Steady-statehematopoieticstemcells’(HSCs)self-renewalanddifferentiationtowardtheirmatureprogenyintheadultbonemarrowistightlyregulatedbycuesfromthemicroenvironment.Recentinsightsintothecellularandmolecularconstituentshaveuncoveredahighlevelofcomplexity.Here,wereviewemergingevidenceshowinghowHSCsandtheirprogenyareregulatedbyaninterdependentnetworkofmesenchymalstromalcells,nervefibers,thevasculature,andalsootherhematopoieticcells.UnderstandingtheinteractionmechanismsintheseintricatenicheswillprovidegreatopportunitiesforHSC-relatedtherapiesandimmunemodulation.INTRODUCTIONThehematopoieticsystemhasanenormouscapabilityofcellproliferationanddifferentiationtomeetthedemandofbloodandimmunecellproductionduringhomeostasisandstress.Allbloodcellsarederivedfromhematopoieticstemcells(HSCs),residingmostlyinthebonemarrow(BM),thatarecapableofself-renewalanddifferentiationintovariousmulti-,oligo-,oruni-potentprogenitors.Progenitorsfurtherproliferateanddiffer-entiateintoadiversearrayoffullyfunctionalmaturecellsintheBMorfollowingmigrationintootherhematopoieticorlymphoidorgans.Thehomeostasisandadaptationofthissystemisahighlydynamicandtightlyregulatedorchestrationofintrinsicprogramsandextrinsicsignalsfromthemicroenvironment,oftenreferredtoas‘‘niche.’’Increasedknowledgehasbeengainedonthemajorcomponentsofthehematopoieticniches.Ithasbecomeclearthatthecuestoorchestratehematopoiesisarehighlycomplexandderivedfromheterogeneouscellularconstit-uents.Abetterunderstandingoftheirmolecularcomponentswilllikelyprovidefuturetherapeuticbenefit.Here,wereviewtherecentadvancesonthenichesforHSCsandtheirimmuno-logicalprogeny,builtonahistoricalperspective...
