Single-cell analysis reveals T cell infiltration in old neurogenic niches

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Abstract

Themammalianbraincontainsneurogenicnichesthatcompriseneuralstemcellsandothercelltypes.Neurogenicnichesbecomelessfunctionalwithage,buthowtheychangeduringageingremainsunclear.Hereweperformsingle-cellRNAsequencingofyoungandoldneurogenicnichesinmice.Theanalysisof14,685single-celltranscriptomesrevealsadecreaseinactivatedneuralstemcells,changesinendothelialcellsandmicroglia,andaninfiltrationofTcellsinoldneurogenicniches.Tcellsinoldbrainsareclonallyexpandedandaregenerallydistinctfromthoseinoldblood,whichsuggeststhattheymayexperiencespecificantigens.Tcellsinoldbrainsalsoexpressinterferon-γ,andthesubsetofneuralstemcellsthathasahighinterferonresponseshowsdecreasedproliferationinvivo.WefindthatTcellscaninhibittheproliferationofneuralstemcellsinco-culturesandinvivo,inpartbysecretinginterferon-γ.OurstudyrevealsaninteractionbetweenTcellsandneuralstemcellsinoldbrains,openingpotentialavenuesthroughwhichtocounteractage-relateddeclineinbrainfunction.

Dataavailability

Allrawsequencingreadsforsingle-cellRNA-seqdata(10xGenomics,Smart-seqv4,andFluidigmC1)aswellasbulkRNA-seqdatacanbefoundunderBioProjectPRJNA450425.Thecommandandconfigurationfiles,inadditiontoalistofallversioneddependenciespresentintherunningenvironment,areavailableintheGithubrepositoryforthispaper(https://github.com/gitbuckley/SingleCellAgingSVZ).

Additionalinformation

Publisher’snote:SpringerNatureremainsneutralwithregardtojurisdictionalclaimsinpublishedmapsandinstitutionalaffiliations.

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