PUBLICATION

R-spondin-1 is required for specification of hematopoietic stem cells through Wnt16 and Vegfa signaling pathways

Authors
Genthe, J.R., Clements, W.K.
ID
ZDB-PUB-170115-5
Date
2017
Source
Development (Cambridge, England)   144(4): 590-600 (Journal)
Registered Authors
Clements, Wilson, Genthe, Jamie
Keywords
Hematopoietic stem cell, R-spondin, Vegfa, Wnt, Zebrafish
MeSH Terms
  • Zebrafish
  • Male
  • Female
  • Signal Transduction
  • Cell Differentiation
  • Hematopoietic Stem Cells/cytology*
  • Zebrafish Proteins/metabolism*
  • Mutation
  • Animals, Genetically Modified
  • Wnt Signaling Pathway
  • Wnt Proteins/metabolism*
  • Body Patterning
  • Protein Isoforms/metabolism
  • Animals
  • Vascular Endothelial Growth Factor A/metabolism*
  • Cloning, Molecular
  • Hemangioblasts/metabolism*
  • Thrombospondins/metabolism*
  • Aorta/metabolism
  • Gene Expression Regulation, Developmental*
(all 20)
PubMed
28087636 Full text @ Development
Abstract
Hematopoietic stem cells (HSCs) are the therapeutic component of bone marrow transplants, but finding immune-compatible donors limits treatment availability and efficacy. Recapitulation of endogenous specification during development is a promising approach to directing HSC specification in vitro, but current protocols are not capable of generating authentic HSCs with high efficiency. Across phyla, HSCs arise from hemogenic endothelium in the ventral floor of the dorsal aorta concurrent with arteriovenous specification and intersegmental vessel (ISV) sprouting, processes regulated by Notch and Wnt. We hypothesized that coordination of HSC specification with vessel patterning might involve modulatory regulatory factors such as R-spondin 1 (Rspo1), an extracellular protein that enhances β-catenin-dependent Wnt signaling and has previously been shown to regulate ISV patterning. We find that Rspo1 is required for HSC specification through control of parallel signaling pathways controlling HSC specification: Wnt16/DeltaC/DeltaD and Vegfa/Tgfβ1. Our results define Rspo1 as a key upstream regulator of two crucial pathways necessary for HSC specification.
Errata / Notes
This article is corrected by ZDB-PUB-220906-128 .
Genes / Markers
Figures
Figure Gallery (12 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
y1TgTransgenic Insertion
    y135
      Point Mutation
      1 - 2 of 2
      Show
      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      Target Reagent Reagent Type
      rspo1MO3-rspo1MRPHLNO
      wnt16MO2-wnt16MRPHLNO
      1 - 2 of 2
      Show
      Fish
      Antibodies
      No data available
      Orthology
      No data available
      Engineered Foreign Genes
      Marker Marker Type Name
      EGFPEFGEGFP
      1 - 1 of 1
      Show
      Mapping
      No data available