Hematopoietic stem cell arrival triggers dynamic remodeling of the perivascular niche

Owen J Tamplin; Ellen M Durand; Logan A Carr; Sarah J Childs; Elliott J Hagedorn; Pulin Li; Amanda D Yzaguirre; Nancy A Speck; Leonard I Zon

doi:10.1016/j.cell.2014.12.032

Hematopoietic stem cell arrival triggers dynamic remodeling of the perivascular niche

Cell. 2015 Jan 15;160(1-2):241-52. doi: 10.1016/j.cell.2014.12.032.

Authors

Owen J Tamplin¹, Ellen M Durand², Logan A Carr¹, Sarah J Childs³, Elliott J Hagedorn¹, Pulin Li⁴, Amanda D Yzaguirre⁵, Nancy A Speck⁵, Leonard I Zon⁶

Affiliations

¹ 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.
² 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.
³ Biochemistry and Molecular Biology, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.
⁴ 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.
⁵ Abramson Family Cancer Research Institute and Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁶ 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.

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:

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Genetically Modified
Cell Division
Core Binding Factor alpha Subunits / genetics
Core Binding Factor alpha Subunits / metabolism
Embryo, Nonmammalian / blood supply
Embryo, Nonmammalian / physiology
Endothelium / cytology
Endothelium / physiology*
Hematopoietic Stem Cells / cytology*
Hematopoietic Stem Cells / physiology
Mesoderm / cytology
Mesoderm / metabolism
Mice
Mice, Inbred C57BL
Stem Cell Niche
Stromal Cells / cytology
Stromal Cells / metabolism
Zebrafish / embryology*
Zebrafish / physiology

Hematopoietic stem cell arrival triggers dynamic remodeling of the perivascular niche

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