PUBLICATION

Hematopoietic stem cell fate is established by the Notch-Runx pathway

Authors
Burns, C.E., Traver, D., Mayhall, E., Shepard, J.L., and Zon, L.I.
ID
ZDB-PUB-050920-8
Date
2005
Source
Genes & Development   19(19): 2331-2342 (Journal)
Registered Authors
Burns (Erter), Caroline, Shepard, Jennifer, Traver, David, Zon, Leonard I.
Keywords
Stem cell, Notch, Runx, AGM, zebrafish, irradiation
MeSH Terms
  • Aorta/cytology
  • Aorta/physiology
  • Cell Differentiation/physiology
  • Mutation
  • Embryonic Development/physiology
  • Embryonic Development/radiation effects
  • Homeostasis/physiology
  • Homeostasis/radiation effects
  • Whole-Body Irradiation/methods
  • Core Binding Factor Alpha 2 Subunit/genetics
  • Core Binding Factor Alpha 2 Subunit/metabolism*
  • Gonads/cytology
  • Gonads/physiology
  • Hematopoiesis/physiology*
  • Hematopoiesis/radiation effects
  • Zebrafish/anatomy & histology
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Animals
  • Gene Expression Regulation, Developmental/physiology
  • Gene Expression Regulation, Developmental/radiation effects
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Hematopoietic Stem Cells/cytology
  • Hematopoietic Stem Cells/metabolism*
  • Gamma Rays
  • Cell Lineage/physiology*
  • Cell Lineage/radiation effects
  • Mesonephros/cytology
  • Mesonephros/physiology
  • Blood Cells/cytology
  • Blood Cells/physiology
PubMed
16166372 Full text @ Genes & Dev.
Abstract
Identifying the molecular pathways regulating hematopoietic stem cell (HSC) specification, self-renewal, and expansion remains a fundamental goal of both basic and clinical biology. Here, we analyzed the effects of Notch signaling on HSC number during zebrafish development and adulthood, defining a critical pathway for stem cell specification. The Notch signaling mutant mind bomb displays normal embryonic hematopoiesis but fails to specify adult HSCs. Surprisingly, transient Notch activation during embryogenesis via an inducible transgenic system led to a Runx1-dependent expansion of HSCs in the aorta-gonad-mesonephros (AGM) region. In irradiated adults, Notch activity induced runx1 gene expression and increased multilineage hematopoietic precursor cells approximately threefold in the marrow. This increase was followed by the accelerated recovery of all the mature blood cell lineages. These data define the Notch-Runx pathway as critical for the developmental specification of HSC fate and the subsequent homeostasis of HSC number, thus providing a mechanism for amplifying stem cells in vivo.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
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Mapping