PUBLICATION

The identification and characterization of zebrafish hematopoietic stem cells

Authors
Ma, D., Zhang, J., Lin, H.F., Italiano, J., and Handin, R.I.
ID
ZDB-PUB-110602-13
Date
2011
Source
Blood   118(2): 289-97 (Journal)
Registered Authors
Handin, Robert, Lin, Hui-feng, Ma, Dongdong
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Blood Platelets/cytology
  • Blood Platelets/metabolism
  • Cell Differentiation/genetics
  • Cell Differentiation/physiology
  • Embryo, Nonmammalian
  • Flow Cytometry
  • Gamma Rays
  • Graft Survival
  • Green Fluorescent Proteins/genetics
  • Green Fluorescent Proteins/metabolism
  • Hematopoiesis/genetics
  • Hematopoiesis/physiology
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells/cytology*
  • Hematopoietic Stem Cells/metabolism
  • Hematopoietic Stem Cells/radiation effects
  • Platelet Membrane Glycoprotein IIb/genetics
  • Zebrafish*/embryology
  • Zebrafish*/genetics
  • Zebrafish*/physiology
PubMed
21586750 Full text @ Blood
Abstract
Hematopoietic stem cells (HSCs) are defined by their ability to self-renew and maintain hematopoiesis throughout the lifespan of an organism. The optical clarity of their embryos and the ease of genetic manipulation make the zebrafish (Danio rerio) an excellent model for studying hematopoiesis. Using flow cytometry, we identified two populations of CD41-GFP+ cells (GFPhi and GFPlo) in the whole kidney marrow of Tg(CD41:GFP) zebrafish. Past studies in humans and mice have shown that CD41 is transiently expressed in the earliest hematopoietic progenitors and is then silenced, reappearing in the platelet/thrombocyte lineage. We have transplanted flow-sorted GFPhi and GFPlo cells into irradiated adult zebrafish and assessed long-term hematopoietic engraftment. Transplantation of GFPhi cells did not reconstitute hematopoiesis. In contrast, we observed multi-lineage hematopoiesis up to 68 weeks after primary and secondary transplantation of GFPlo cells. We detected the CD41-GFP transgene in all major hematopoietic lineages and CD41-GFP+ cells in histologic sections of kidneys from transplant recipients. These studies show that CD41-GFPlo cells fulfill generally accepted criteria for HSCs. The identification of fluorescent zebrafish HSCs, coupled with our ability to transplant them into irradiated adult recipients provide a valuable new tool to track HSC homing, proliferation and differentiation into hematopoietic cells.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping