Guo, BinHuang, XinxinCooper, ScottBroxmeyer, Hal E.2018-08-022018-08-022017-04Guo, B., Huang, X., Cooper, S., & Broxmeyer, H. E. (2017). Glucocorticoid hormone-induced chromatin remodeling enhances human hematopoietic stem cell homing and engraftment. Nature Medicine, 23(4), 424–428. http://doi.org/10.1038/nm.4298https://hdl.handle.net/1805/16955Efficient hematopoietic stem cell (HSC) homing is important for hematopoietic cell transplantation (HCT), especially when HSC numbers are limited, as in the use of cord blood (CB). In a screen of small-molecule compounds, we identified glucocorticoid (GC) hormone signaling as an activator of CXCR4 expression in human CB HSCs and hematopoietic progenitor cells (HPCs). Short-term GC pretreatment of human CB HSCs and HPCs promoted SDF-1-CXCR4-axis-mediated chemotaxis, homing, and long-term engraftment when these cells were transplanted into primary- and secondary-recipient NSG mice. Mechanistically, activated glucocorticoid receptor binds directly to a glucocorticoid response element in the CXCR4 promoter and recruits the SRC-1-p300 complex to promote H4K5 and H4K16 histone acetylation, facilitating transcription of CXCR4. These results suggest a new and readily available means to enhance the clinical efficacy of CB HCT.en-USPublisher PolicyAcetylationBlotting, WesternChemotaxisChromatin assembly and disassembly/drug effectsChromatin immunoprecipitationE1A-associated p300 proteinFetal bloodFlow cytometryGlucocorticoidsHematopoietic stem cell transplantationNuclear receptor coactivator 2Article