title: CXCR1 remodels the vascular niche to promote hematopoietic stem and progenitor cell engraftment.
abstract: The microenvironment is an important regulator of hematopoietic stem and progenitor cell (HSPC) biology. Recent advances marking fluorescent HSPCs have allowed exquisite visualization of HSPCs in the caudal hematopoietic tissue (CHT) of the developing zebrafish. Here, we show that the chemokinecxcl8and its receptor,cxcr1, are expressed by zebrafish endothelial cells, and we identifycxcl8/cxcr1signaling as a positive regulator of HSPC colonization. Single-cell tracking experiments demonstrated that this is a result of increases in HSPC-endothelial cell "cuddling," HSPC residency time within the CHT, and HSPC mitotic rate. Enhancedcxcl8/cxcr1signaling was associated with an increase in the volume of the CHT and induction ofcxcl12aexpression. Finally, using parabiotic zebrafish, we show thatcxcr1acts HSPC nonautonomously to improve the efficiency of donor HSPC engraftment. This work identifies a mechanism by which the hematopoietic niche remodels to promote HSPC engraftment and suggests thatcxcl8/cxcr1signaling is a potential therapeutic target in patients undergoing hematopoietic stem cell transplantation.
authors.affiliation: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA 02138.
authors.forename: Bradley W
authors.initials: BW
authors.lastname: Blaser
authors.affiliation: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA 02138.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Moore
authors.affiliation: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA 02138.
authors.forename: Elliott J
authors.initials: EJ
authors.lastname: Hagedorn
authors.affiliation: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA 02138.
authors.forename: Brian
authors.initials: B
authors.lastname: Li
authors.affiliation: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA 02138.
authors.forename: Raquel
authors.initials: R
authors.lastname: Riquelme
authors.affiliation: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA 02138.
authors.forename: Asher
authors.identifier: 0000-0001-6190-8934
authors.initials: A
authors.lastname: Lichtig
authors.affiliation: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA 02138.
authors.forename: Song
authors.initials: S
authors.lastname: Yang
authors.affiliation: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA 02138.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, The University of Illinois College of Medicine, Chicago, IL 60612.
authors.forename: Owen J
authors.initials: OJ
authors.lastname: Tamplin
authors.affiliation: Department of Hematology and Oncology, Dr. von Hauner Children's Hospital, Ludwig-Maximilians University, 80539 Munich, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Binder
authors.affiliation: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA 02138 zon@enders.tch.harvard.edu.
authors.forename: Leonard I
authors.identifier: 0000-0003-0860-926X
authors.initials: LI
authors.lastname: Zon
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000502:physiology; D016209:Interleukin-8 / Q000502:physiology; D023062:Receptors, Interleukin-8A / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D015027:Zebrafish
chemical_list: D016209:Interleukin-8; D023062:Receptors, Interleukin-8A