Pharmacologic increase in HIF1α enhances hematopoietic stem and progenitor homing and engraftment

dc.contributor.authorSpeth, Jennifer M.
dc.contributor.authorHoggatt, Jonathan
dc.contributor.authorSingh, Pratibha
dc.contributor.authorPelus, Louis M.
dc.contributor.departmentDepartment of Microbiology and Immunology, IU School of Medicineen_US
dc.date.accessioned2016-05-11T15:58:38Z
dc.date.available2016-05-11T15:58:38Z
dc.date.issued2014-01-09
dc.description.abstractHematopoietic stem cell (HSC) transplantation is a lifesaving therapy for a number of immunologic disorders. For effective transplant, HSCs must traffic from the peripheral blood to supportive bone marrow niches. We previously showed that HSC trafficking can be enhanced by ex vivo treatment of hematopoietic grafts with 16-16 dimethyl prostaglandin E2 (dmPGE2). While exploring regulatory molecules involved in dmPGE2 enhancement, we found that transiently increasing the transcription factor hypoxia-inducible factor 1-α (HIF1α) is required for dmPGE2-enhanced CXCR4 upregulation and enhanced migration and homing of stem and progenitor cells and that pharmacologic manipulation of HIF1α is also capable of enhancing homing and engraftment. We also now identify the specific hypoxia response element required for CXCR4 upregulation. These data define a precise mechanism through which ex vivo pulse treatment with dmPGE2 enhances the function of hematopoietic stem and progenitor cells; these data also define a role for hypoxia and HIF1α in enhancement of hematopoietic transplantation.en_US
dc.identifier.citationSpeth, J. M., Hoggatt, J., Singh, P., & Pelus, L. M. (2014). Pharmacologic increase in HIF1α enhances hematopoietic stem and progenitor homing and engraftment. Blood, 123(2), 203–207. http://doi.org/10.1182/blood-2013-07-516336en_US
dc.identifier.issn1528-0020en_US
dc.identifier.urihttps://hdl.handle.net/1805/9567
dc.language.isoen_USen_US
dc.publisherAmerican Society of Hematologyen_US
dc.relation.isversionof10.1182/blood-2013-07-516336en_US
dc.relation.journalBlooden_US
dc.rightsPublisher Policyen_US
dc.sourcePMCen_US
dc.subjectDinoprostoneen_US
dc.subjectpharmacologyen_US
dc.subjectHematopoietic Stem Cell Mobilizationen_US
dc.subjectHematopoietic Stem Cell Transplantationen_US
dc.subjectHematopoietic Stem Cellsen_US
dc.subjectdrug effectsen_US
dc.subjectmetabolismen_US
dc.subjectHypoxia-Inducible Factor 1, alpha Subuniten_US
dc.subjectGeneticsen_US
dc.titlePharmacologic increase in HIF1α enhances hematopoietic stem and progenitor homing and engraftmenten_US
dc.typeArticleen_US
ul.alternative.fulltexthttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3888286/en_US
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