ZFIN ID: ZDB-PUB-170115-5
R-spondin-1 is required for specification of hematopoietic stem cells through Wnt16 and Vegfa signaling pathways
Genthe, J.R., Clements, W.K.
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:
  • Animals
  • Animals, Genetically Modified
  • Aorta/metabolism
  • Body Patterning
  • Cell Differentiation
  • Cloning, Molecular
  • Female
  • Gene Expression Regulation, Developmental*
  • Hemangioblasts/metabolism*
  • Hematopoietic Stem Cells/cytology*
  • Male
  • Mutation
  • Protein Isoforms/metabolism
  • Signal Transduction
  • Thrombospondins/metabolism*
  • Vascular Endothelial Growth Factor A/metabolism*
  • Wnt Proteins/metabolism*
  • Wnt Signaling Pathway
  • Zebrafish
  • Zebrafish Proteins/metabolism*
PubMed: 28087636 Full text @ Development
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.