PUBLICATION

Hematopoietic Stem Cell Arrival Triggers Dynamic Remodeling of the Perivascular Niche

Authors
Tamplin, O.J., Durand, E.M., Carr, L.A., Childs, S.J., Hagedorn, E.J., Li, P., Yzaguirre, A.D., Speck, N.A., Zon, L.I.
ID
ZDB-PUB-150117-1
Date
2015
Source
Cell   160: 241-252 (Journal)
Registered Authors
Childs, Sarah J., Tamplin, Owen, Zon, Leonard I.
Keywords
none
Datasets
GEO:GSE56015
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
PubMed
25594182 Full text @ Cell
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:
Genes / Markers
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes