title: Hematopoietic stem cell arrival triggers dynamic remodeling of the perivascular niche.
abstract: Hematopoietic stem and progenitor cells (HSPCs) can reconstitute and sustain the entire blood system. We generated a highly specific transgenic reporter of HSPCs in zebrafish. This allowed us to perform high-resolution live imaging on endogenous HSPCs not currently possible in mammalian bone marrow. Using this system, we have uncovered distinct interactions between single HSPCs and their niche. When an HSPC arrives in the perivascular niche, a group of endothelial cells remodel to form a surrounding pocket. This structure appears conserved in mouse fetal liver. Correlative light and electron microscopy revealed that endothelial cells surround a single HSPC attached to a single mesenchymal stromal cell. Live imaging showed that mesenchymal stromal cells anchor HSPCs and orient their divisions. A chemical genetic screen found that the compound lycorine promotes HSPC-niche interactions during development and ultimately expands the stem cell pool into adulthood. Our studies provide evidence for dynamic niche interactions upon stem cell colonization. PAPERFLICK:
authors.affiliation: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Owen J
authors.initials: OJ
authors.lastname: Tamplin
authors.affiliation: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA; Biological and Biomedical Sciences, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Durand
authors.affiliation: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Logan A
authors.initials: LA
authors.lastname: Carr
authors.affiliation: Biochemistry and Molecular Biology, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Childs
authors.affiliation: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
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 Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA; Chemical Biology Program, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Pulin
authors.initials: P
authors.lastname: Li
authors.affiliation: Abramson Family Cancer Research Institute and Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Amanda D
authors.initials: AD
authors.lastname: Yzaguirre
authors.affiliation: Abramson Family Cancer Research Institute and Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Speck
authors.affiliation: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA; Biological and Biomedical Sciences, Harvard University, Cambridge, MA 02138, USA; Chemical Biology Program, Harvard University, Cambridge, MA 02138, USA. Electronic address: zon@enders.tch.harvard.edu.
authors.forename: Leonard I
authors.initials: LI
authors.lastname: Zon
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002455:Cell Division; D050657:Core Binding Factor alpha Subunits / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000098:blood supply / Q000502:physiology; D004727:Endothelium / Q000166:cytology / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D055153:Stem Cell Niche; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000502:physiology
chemical_list: D050657:Core Binding Factor alpha Subunits