Withtheexceptionofmatureerythrocytes,cellswithinthehumanhematopoieticsystemarecharacterizedbythecellsurfaceexpressionofthepan-leukocytereceptorCD45.Here,weidentifyanovelsubsetamongmononuclearcordbloodcellsdepletedoflineagecommitmentmarkers(Lin-)thataredevoidofCD45expression.Surprisingly,functionalexaminationofLin-CD45-cellsalsolackingcellsurfaceCD34revealedtheywerecapableofmultipotentialhematopoieticprogenitorcapacity.Co-culturewithmouseembryoniclimbbudcellsdemonstratedthatLin-CD45-CD34-cellswerecapableofcontributingtocartilagenodulesanddifferentiatingintohumanchondrocytes.BMP-4,amesodermalfactorknowntopromotechondrogenesis,significantlyaugmentedLin-CD45-CD34-differentiationintochondrocytes.Moreover,unlikeCD34+humanhematopoieticstemcells,Lin-CD45-CD34-cellswereunabletoproliferateorsurviveinliquidcultures,whereassingleLin-CD45-CD34-cellswereabletochimerizetheinnercellmass(ICM)ofmurineblastocystsandproliferateinthisembryonicenvironment.OurstudyidentifiesanovelpopulationofLin-CD45-CD34-cellscapableofcommitmentintobothhematopoieticandchondrocyticlineages,suggestingthathumancordbloodmayprovideamoreubiquitoussourceoftissuewithbroaderdevelopmentalpotentialthanpreviouslyappreciated.
