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We are analyzing https://www.nature.com/articles/nature01593.

Title:
A role for Wnt signalling in self-renewal of haematopoietic stem cells | Nature
Description:
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.
Website Age:
30 years and 10 months (reg. 1994-08-11).

Matching Content Categories {📚}

  • Education
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Custom-built

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$63,100 per month
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Keywords {🔍}

pubmed, article, google, scholar, cas, nature, stem, cells, cell, wnt, hematopoietic, weissman, βcatenin, ads, signaling, central, access, usa, signalling, pathway, content, reya, axin, development, research, cookies, role, regulation, proc, natl, acad, sci, cancer, privacy, haematopoietic, hscs, hsc, vivo, proliferation, science, med, wingless, stanford, supplementary, data, information, selfrenewal, tannishtha, duncan, domen,

Topics {✒️}

nature portfolio permissions reprints privacy policy cancer research institute advertising leukemia research foundation promotes gsk-3β-dependent phosphorylation social media β-catenin/tcf-4 complex imposes health research nature immunol nature genet subscribe nature nature biotechnol research epithelia stem-cell compartments nature med long-term repopulating subset high-fidelity mrna amplification induce anchorage-independent growth glycogen synthase kinase-3β frizzled ligand-binding domain hydrogel-based microenvironment engineering kitl/c-kit signaling cell factor-activated transcription fzd8-crd igg construct nature 372 nature 414 nature 423 nature activated β-catenin expands haematopoietic stem cells system-level model reveals author correspondence stem cell differentiation modified lef-1/tcf elements β-catenin-tcf complex personal data β-catenin-mediated transcription springerlink instant access data protection permissions hematopoietic stem cells long-term cultures multilineage progenitor cells cancer stem cells article reya jos domen wnt signaling pathway de los santos

Schema {🗺️}

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         description: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.
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      headline:A role for Wnt signalling in self-renewal of haematopoietic stem cells
      description: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.
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