A role for Wnt signalling in self-renewal of haematopoietic stem cells
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 beta-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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TCF1 is one of the targets of canonical Wnt signalling, which maintains stemness in adult tissue stem cells, tumours, and peripheral T cells.
“TCF1 is one of the targets of canonical Wnt signalling, which maintains stemness in adult tissue stem cells, tumours, and peripheral T cells14,15.”
From An autoimmune stem-like CD8 T cell population drives type 1 diabetes (2022) · cites this paper as [15]
Aging of hematopoietic stem cells is associated with low canonical Wnt signaling.
“Our findings are in line with mechanisms of aging in the HSC compartment (Florian et al., 2013), in which aging of HSCs is also associated with low canonical Wnt signaling (Reya et al., 2003).”
From Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells (2017) · cites this paper as Reya et al., 2003
The findings on intestinal stem cell aging are in line with mechanisms of aging in the hematopoietic stem cell compartment, where aging is associated with low canonical Wnt signaling.
“Our findings are in line with mechanisms of aging in the HSC compartment (Florian et al., 2013), in which aging of HSCs is also associated with low canonical Wnt signaling (Reya et al., 2003).”
From Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells (2017) · cites this paper as Reya et al., 2003
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EGFR is required for Wnt9a/Fzd9b signalling specificity in haematopoietic stem cells
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- Authors
- Reya, T., Duncan, A. W., Ailles, L., Domen, J., Scherer, D. C., Willert, K., Hintz, L., Nusse, R., & Weissman, I. L.
- Affiliations
- Duke University (US)
- Stanford Medicine (US)
- Duke Medical Center (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Reya, Tannishtha
- Venue
- Nature
- Published
- 2003-04-27
- Volume
- 423
- Issue
- 6938
- Pages
- 409-414
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2118453722
- Cited by
- 2,159
- References
- 45
- Citations by year
- 2026: 20 · 2025: 29 · 2024: 41 · 2023: 40 · 2022: 40 · 2021: 53 · 2020: 55 · 2019: 64 · 2018: 53 · 2017: 78 · 2016: 77 · 2015: 82 · 2014: 95 · 2013: 98 · 2012: 137
- FWCI
- 87.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- Wnt signaling, hematopoietic stem cells, self-renewal, β-catenin, Axin, HOXB4, Notch1, HSC homeostasis, long-term culture, haematopoietic reconstitution
- MeSH terms
- Animals, Cell Division, Cytoskeletal Proteins, DNA-Binding Proteins, Hematopoietic Stem Cells, Membrane Proteins, Proto-Oncogene Proteins, Receptors, Cell Surface, Transcription Factors, Signal Transduction, Trans-Activators, Zebrafish Proteins, Wnt Proteins, beta Catenin, Mice, Lymphoid Enhancer-Binding Factor 1, Receptor, Notch1
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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