PUBLICATION

Live imaging of Runx1 expression in the dorsal aorta tracks the emergence of blood progenitors from endothelial cells

Authors
Lam, E.Y., Hall, C.J., Crosier, P.S., Crosier, K.E., and Flores, M.V.
ID
ZDB-PUB-100511-23
Date
2010
Source
Blood   116(6): 909-914 (Journal)
Registered Authors
Crosier, Phil, Flores, Maria, Hall, Chris, Lam, Enid
Keywords
none
MeSH Terms
  • Animals
  • Aorta*/cytology
  • Aorta*/embryology
  • Aorta*/physiology
  • Cell Differentiation/physiology
  • Core Binding Factor Alpha 2 Subunit/genetics
  • Core Binding Factor Alpha 2 Subunit/metabolism*
  • Endothelial Cells/cytology
  • Endothelial Cells/physiology*
  • Epidermal Growth Factor/genetics
  • Epidermal Growth Factor/metabolism
  • Female
  • Gene Expression Regulation, Developmental
  • Green Fluorescent Proteins/genetics
  • Hematopoiesis/physiology
  • Hematopoietic Stem Cells/cytology
  • Hematopoietic Stem Cells/physiology*
  • Kidney/cytology
  • Kidney/embryology
  • Kidney/physiology
  • Male
  • Regional Blood Flow/physiology
  • Thymus Gland/cytology
  • Thymus Gland/embryology
  • Thymus Gland/physiology
  • Transcriptional Activation/physiology
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
20453160 Full text @ Blood
Abstract
Blood cells of an adult vertebrate are continuously generated by hematopoietic stem cells (HSCs) that originate during embryonic life within the aorta-gonad-mesonephros (AGM) region. There is now compelling in vivo evidence that HSCs are generated from aortic endothelial cells, and that this process is critically regulated by the transcription factor Runx1. By time-lapse microscopy of Runx1-Enhanced Green Fluorescent Protein (EGFP) transgenic zebrafish embryos, we were able to capture a subset of cells within the ventral endothelium of the dorsal aorta (DA), as they acquire hemogenic properties, and directly emerge as presumptive HSCs. These nascent hematopoietic cells assume a rounded morphology, transiently occupy the sub-aortic space, and eventually enter the circulation via the caudal vein. Cell tracing showed that these cells subsequently populated the sites of definitive hematopoiesis (thymus and kidney), consistent with an HSC identity. HSC numbers depended on activity of the transcription factor Runx1, on blood flow, and on proper development of the DA; features in common with mammals. This study captures the earliest events of the transition of endothelial cells to a hemogenic endothelium, and demonstrates that embryonic haematopoietic progenitors directly differentiate from endothelial cells within a living organism.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping