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Hematopoietic stem cell development requires transient Wnt/β-catenin activity
Cristina Ruiz-Herguido1, Jordi Guiu, Teresa D'Altri
1Program in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques, Parc de Recerca Biomèdica de Barcelona, 08003 Barcelona, Spain.
The Journal of Experimental Medicine
|July 18, 2012
Summary
Wnt/β-catenin signaling is essential for generating hematopoietic stem cells (HSCs) from embryonic endothelial cells in the aorta-gonad-mesonephros region. This pathway is crucial for HSC emergence but not their long-term maintenance.
Area of Science:
- Developmental biology
- Stem cell biology
- Regenerative medicine
Background:
- Hematopoietic stem cells (HSCs) are vital for blood formation and regenerative medicine.
- HSCs originate from endothelial cells in the aorta-gonad-mesonephros (AGM) region during embryonic development.
- Understanding HSC generation is key for in vitro HSC production.
Purpose of the Study:
- To investigate the role of Wnt/β-catenin signaling in HSC emergence from embryonic endothelial precursors.
- To determine the necessity of β-catenin activity in the aorta-gonad-mesonephros region for HSC generation.
- To explore the potential of targeting Wnt/β-catenin for in vitro HSC production.
Main Methods:
- Analysis of β-catenin localization and activity in embryonic mouse aorta.
- Genetic deletion of β-catenin in embryonic endothelium (VE-cadherin-Cre) and hematopoietic cells (Vav1-Cre).
- In vitro differentiation of hematopoietic cells from AGM endothelial precursors.
Main Results:
- Nuclear β-catenin was detected in endothelial cells associated with early hematopoietic clusters in the embryonic aorta.
- Transient Wnt/β-catenin activity in the AGM region is required for generating long-term HSCs and in vitro hematopoietic cells.
- Genetic deletion of β-catenin in embryonic endothelium blocked HSC emergence but not adult endothelium contribution.
- Deletion in hematopoietic cells did not affect HSC emergence.
Conclusions:
- Wnt/β-catenin signaling is indispensable for the emergence of HSCs from embryonic endothelial cells.
- This signaling pathway is required for HSC generation in the aorta-gonad-mesonephros region.
- Wnt/β-catenin activity is necessary for HSC emergence, not for their subsequent maintenance.
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