Glucocorticoid hormone-induced chromatin remodeling enhances human hematopoietic stem cell homing and engraftment
dc.contributor.author | Guo, Bin | |
dc.contributor.author | Huang, Xinxin | |
dc.contributor.author | Cooper, Scott | |
dc.contributor.author | Broxmeyer, Hal E. | |
dc.contributor.department | Microbiology and Immunology, School of Medicine | en_US |
dc.date.accessioned | 2018-08-02T18:39:44Z | |
dc.date.available | 2018-08-02T18:39:44Z | |
dc.date.issued | 2017-04 | |
dc.description.abstract | Efficient 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_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Guo, 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.4298 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/16955 | |
dc.language.iso | en_US | en_US |
dc.publisher | Nature Publishing Group | en_US |
dc.relation.isversionof | 10.1038/nm.4298 | en_US |
dc.relation.journal | Nature Medicine | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | Acetylation | en_US |
dc.subject | Blotting, Western | en_US |
dc.subject | Chemotaxis | en_US |
dc.subject | Chromatin assembly and disassembly/drug effects | en_US |
dc.subject | Chromatin immunoprecipitation | en_US |
dc.subject | E1A-associated p300 protein | en_US |
dc.subject | Fetal blood | en_US |
dc.subject | Flow cytometry | en_US |
dc.subject | Glucocorticoids | en_US |
dc.subject | Hematopoietic stem cell transplantation | en_US |
dc.subject | Nuclear receptor coactivator 2 | en_US |
dc.title | Glucocorticoid hormone-induced chromatin remodeling enhances human hematopoietic stem cell homing and engraftment | en_US |
dc.type | Article | en_US |