Neutralizing negative epigenetic regulation by HDAC5 enhances human haematopoietic stem cell homing and engraftment
dc.contributor.author | Huang, Xinxin | |
dc.contributor.author | Guo, Bin | |
dc.contributor.author | Liu, Sheng | |
dc.contributor.author | Wan, Jun | |
dc.contributor.author | Broxmeyer, Hal E. | |
dc.contributor.department | Microbiology and Immunology, School of Medicine | en_US |
dc.date.accessioned | 2019-05-07T14:25:01Z | |
dc.date.available | 2019-05-07T14:25:01Z | |
dc.date.issued | 2018-07-16 | |
dc.description.abstract | Enhancement of hematopoietic stem cell (HSC) homing and engraftment is clinically critical, especially for cord blood (CB) hematopoietic cell transplantation. Here we report that specific HDAC5 inhibition highly upregulates CXCR4 surface expression in human CB HSCs and progenitor cells (HPCs). This results in enhanced SDF-1/CXCR4-mediated chemotaxis and increased homing to the bone marrow environment, with elevated SCID-repopulating cell (SRC) frequency and enhanced long-term and secondary engraftment in NSG mice. HDAC5 inhibition increases acetylated p65 levels in the nucleus, which is important for CXCR4 transcription. Inhibition of nuclear factor-κB (NF-κB) signaling suppresses HDAC5-mediated CXCR4 upregulation, enhanced HSC homing, and engraftment. Furthermore, activation of the NF-κB signaling pathway via TNFα also results in significantly increased CXCR4 surface expression, enhanced HSC homing, and engraftment. These results demonstrate a previously unknown negative epigenetic regulation of HSC homing and engraftment by HDAC5, and allow for a new and simple translational strategy to enhance HSC transplantation. | en_US |
dc.eprint.version | Final published version | en_US |
dc.identifier.citation | Huang, X., Guo, B., Liu, S., Wan, J., & Broxmeyer, H. E. (2018). Neutralizing negative epigenetic regulation by HDAC5 enhances human haematopoietic stem cell homing and engraftment. Nature communications, 9(1), 2741. doi:10.1038/s41467-018-05178-5 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/19152 | |
dc.language.iso | en_US | en_US |
dc.publisher | Nature Publishing Group | en_US |
dc.relation.isversionof | 10.1038/s41467-018-05178-5 | en_US |
dc.relation.journal | Nature communications | en_US |
dc.rights | Attribution 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
dc.source | PMC | en_US |
dc.subject | Chemokine CXCL12 | en_US |
dc.subject | Chemotaxis | en_US |
dc.subject | Cord Blood Stem Cell Transplantation | en_US |
dc.subject | Epigenesis, Genetic | en_US |
dc.subject | Fetal Blood | en_US |
dc.subject | Graft Survival | en_US |
dc.subject | Hematopoietic Stem Cell Transplantation | en_US |
dc.subject | Histone Deacetylases | en_US |
dc.subject | Mice, Inbred NOD | en_US |
dc.subject | Primary Cell Culture | en_US |
dc.subject | RNA, Small Interfering | en_US |
dc.subject | Receptors, CXCR4 | en_US |
dc.subject | Signal Transduction | en_US |
dc.subject | Transcription Factor RelA | en_US |
dc.subject | Transplantation, Heterologous | en_US |
dc.subject | Tumor Necrosis Factor-alpha | en_US |
dc.title | Neutralizing negative epigenetic regulation by HDAC5 enhances human haematopoietic stem cell homing and engraftment | en_US |
dc.type | Article | en_US |
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