424VOLUME23|NUMBER4|APRIL2017naturemedicinebriefcommunicationsHSCs,whichgiverisetoallbloodcelltypes,areessentialforsuccess-fulHCT1.CBisincreasinglybeingemployedasasourceofHSCsforHCT2,whichisusedtotreatpatientswithbothmalignantandnon-malignanthematologicaldisorders.OnelimitationtogreaterusageofCBforHCTisthatHSCsarepresentinonlylimitednumbersinasingleunitofCB3.AlthoughexvivoexpansionofHSCsiscurrentlybeingassessedasamethodtoenhanceCBHCT3–5,anothermeanstoimprovesingle-CB-unitHCTistoenhancethehoming,andthustheengraftmentefficiency,ofHSCs.IntravenouslyinfusedHSCstraffictobonemarrow(BM)andimplantinmicroenvironmentalniches,wheretheyarenurturedtopromoteself-renewalanddifferentiation6.TheSDF-1–CXCR4chem-otacticaxisisamajorpathwaythatdirectsthemigrationandhomingofHSCsfromperipheralblood(PB)toBMniches7,8.BymodulatingtheinterplaybetweenSDF-1andCXCR4,HSChomingefficiencycanbeimproved.Forexample,dipeptidylpeptidase-4(DPP4)inhibitionblocksproteolyticinactivationofSDF-1andenhancesengraftmentofHSCs9,treatmentwithprostaglandinE2(PGE2)orvalproicacidfacili-tatesHSCchemotaxistowardSDF-1gradientsbyupregulatingCXCR4cellsurfaceexpression10–12,andmildheatexposurepromotesincor-porationofCXCR4intolipidrafts,thusenhancingHSCchemotaxisandengraftment13.However,thereisstillaneedforothermethodsthatcanenhancehomingandengraftmentofHSCs.SmallsyntheticmoleculeshavebeenevaluatedfortheireffectsonHSCfunction3–5.ToidentifycompoundsthatmightbeusefulforincreasingHSChomingefficiency,weperformedasmall-scalecom-poundscreenformoleculesthatcanupregulatesurfaceexpressionofCXCR4onhumanCBCD34+cells.Usinganuclearhormoneligandlibraryincluding74chemicalcompounds(SupplementaryTable1),wefoundthattreatmentofCBCD34+cellsfor16hwithdexametha-sone(Dex),asyntheticGC,greatlypromotedcellsurfaceexpressionofCXCR4(Fig.1a).ExpressionofCXCR4onCBCD34+cellswasalsoincreasedaftertreatingcellswithotherGCs(whichwerenotpresentinthelibrary),includingFlonase(fluticasonepropionate),cortisol(hydrocortisone),andMedrol(methylprednisolone)(F...
