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A role for Wnt signalling in self-renewal of haematopoietic stem cells

Author

Listed:
  • Tannishtha Reya

    (Duke University Medical Center)

  • Andrew W. Duncan

    (Duke University Medical Center)

  • Laurie Ailles

    (Stanford University School of Medicine)

  • Jos Domen

    (Duke University Medical Center)

  • David C. Scherer

    (Stanford University School of Medicine)

  • Karl Willert

    (Stanford University School of Medicine)

  • Lindsay Hintz

    (Duke University Medical Center)

  • Roel Nusse

    (Stanford University School of Medicine)

  • Irving L. Weissman

    (Stanford University School of Medicine)

Abstract

Haematopoietic stem cells (HSCs) have the ability to renew themselves and to give rise to all lineages of the blood; however, the signals that regulate HSC self-renewal remain unclear. Here we show that the Wnt signalling pathway has an important role in this process. Overexpression of activated β-catenin expands the pool of HSCs in long-term cultures by both phenotype and function. Furthermore, HSCs in their normal microenvironment activate a LEF-1/TCF reporter, which indicates that HCSs respond to Wnt signalling in vivo. To demonstrate the physiological significance of this pathway for HSC proliferation we show that the ectopic expression of axin or a frizzled ligand-binding domain, inhibitors of the Wnt signalling pathway, leads to inhibition of HSC growth in vitro and reduced reconstitution in vivo. Furthermore, activation of Wnt signalling in HSCs induces increased expression of HoxB4 and Notch1, genes previously implicated in self-renewal of HSCs. We conclude that the Wnt signalling pathway is critical for normal HSC homeostasis in vitro and in vivo, and provide insight into a potential molecular hierarchy of regulation of HSC development.

Suggested Citation

  • Tannishtha Reya & Andrew W. Duncan & Laurie Ailles & Jos Domen & David C. Scherer & Karl Willert & Lindsay Hintz & Roel Nusse & Irving L. Weissman, 2003. "A role for Wnt signalling in self-renewal of haematopoietic stem cells," Nature, Nature, vol. 423(6938), pages 409-414, May.
    • Handle: RePEc:nat:nature:v:423:y:2003:i:6938:d:10.1038_nature01593
    DOI: 10.1038/nature01593
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    Cited by:

    1. Wenxue Ma & Alejandro Gutierrez & Daniel J Goff & Ifat Geron & Anil Sadarangani & Christina A M Jamieson & Angela C Court & Alice Y Shih & Qingfei Jiang & Christina C Wu & Kang Li & Kristen M Smith & , 2012. "NOTCH1 Signaling Promotes Human T-Cell Acute Lymphoblastic Leukemia Initiating Cell Regeneration in Supportive Niches," PLOS ONE, Public Library of Science, vol. 7(6), pages 1-14, June.
    2. Yang Liu & Qi Chen & Hyun-Woo Jeong & Bong Ihn Koh & Emma C. Watson & Cong Xu & Martin Stehling & Bin Zhou & Ralf H. Adams, 2022. "A specialized bone marrow microenvironment for fetal haematopoiesis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Rongli Sun & Juan Zhang & Mengzhen Xiong & Haiyan Wei & Kehong Tan & Lihong Yin & Yuepu Pu, 2015. "Altered Expression of Genes in Signaling Pathways Regulating Proliferation of Hematopoietic Stem and Progenitor Cells in Mice with Subchronic Benzene Exposure," IJERPH, MDPI, vol. 12(8), pages 1-16, August.

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