The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Defining the Role of Wnt/β‐Catenin Signaling in the Survival, Proliferation, and Self‐Renewal of Human Embryonic Stem Cells
Abstract
We used a panel of human and mouse fibroblasts with various abilities for supporting the prolonged growth of human embryonic stem cells (hESCs) to elucidate growth factors required for hESC survival, proliferation, and maintenance of the undifferentiated and pluripotent state (self-renewal). We found that supportive feeder cells secrete growth factors required for both hESC survival/proliferation and blocking hESC spontaneous differentiation to achieve self-renewal. The antidifferentiation soluble factor is neither leukemia inhibitory factor nor Wnt, based on blocking experiments using their antagonists. Because Wnt/beta-catenin signaling has been implicated in cell-fate determination and stem cell expansion, we further examined the effects of blocking or adding recombinant Wnt proteins on undifferentiated hESCs. In the absence of feeder cell-derived factors, hESCs cultured under a feeder-free condition survived/proliferated poorly and gradually differentiated. Adding recombinant Wnt3a stimulated hESC proliferation but also differentiation. After 4-5 days of Wnt3a treatment, hESCs that survived maintained the undifferentiated phenotype but few could form undifferentiated hESC colonies subsequently. Using a functional reporter assay, we found that the beta-catenin-mediated transcriptional activation in the canonical Wnt pathway was minimal in undifferentiated hESCs, but greatly upregulated during differentiation induced by the Wnt treatment and several other methods. Thus, Wnt/beta-catenin activation does not suffice to maintain the undifferentiated and pluripotent state of hESCs. We propose a new model for the role of Wnt/beta-catenin signaling in undifferentiated hESCs.
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Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860
Multilineage potential of adult human mesenchymal stem cells
Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., Moorman, M. A., Simonetti, D. W., Craig, S., & Marshak, D. R. (1999) · Science · doi:10.1126/science.284.5411.143 · Cited by 21,052
Wnt proteins are lipid-modified and can act as stem cell growth factors
Willert, K., Brown, J. D., Danenberg, E., Duncan, A. W., Weissman, I. L., Reya, T., Yates, J. R., & Nusse, R. (2003) · Nature · doi:10.1038/nature01611 · Cited by 2,257
A role for Wnt signalling in self-renewal of haematopoietic stem cells
Reya, T., Duncan, A. W., Ailles, L., Domen, J., Scherer, D. C., Willert, K., Hintz, L., Nusse, R., & Weissman, I. L. (2003) · Nature · doi:10.1038/nature01593 · Cited by 2,159
Defining the Epithelial Stem Cell Niche in Skin
Tumbar, T., Guasch, G., Greco, V., Blanpain, C., Lowry, W. E., Rendl, M., & Fuchs, E. (2004) · Science · doi:10.1126/science.1092436 · Cited by 2,031
WNT and β-catenin signalling: diseases and therapies
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Zebrafish Prickle, a Modulator of Noncanonical Wnt/Fz Signaling, Regulates Gastrulation Movements
Veeman, M. T., Slusarski, D. C., Kaykas, A., Louie, S. H., & Moon, R. T. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00240-9 · Cited by 945
Apc modulates embryonic stem-cell differentiation by controlling the dosage of β-catenin signaling
Kielman, M. F., Rindapää, M., Gaspar, C., van Poppel, N., Breukel, C., van Leeuwen, S., Taketo, M. M., Roberts, S., Smits, R., & Fodde, R. (2002) · Nature Genetics · doi:10.1038/ng1045 · Cited by 362
Cited by
Lian, X., Hsiao, C., Wilson, G., Zhu, K., Hazeltine, L. B., Azarin, S. M., Raval, K. K., Zhang, J., Kamp, T. J., & Palecek, S. P. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1200250109 · Cited by 1,717
Derivation of blood-brain barrier endothelial cells from human pluripotent stem cells
Lippmann, E. S., Azarin, S. M., Kay, J. E., Nessler, R. A., Wilson, H. K., Al-Ahmad, A., Palecek, S. P., & Shusta, E. V. (2012) · Nature Biotechnology · doi:10.1038/nbt.2247 · Cited by 800
Targeting Wnt Signaling: Can We Safely Eradicate Cancer Stem Cells?
Takahashi-Yanaga, F., & Kahn, M. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-2943 · Cited by 499
Xiao, L., Yuan, X., & Sharkis, S. J. (2006) · Stem Cells · doi:10.1634/stemcells.2005-0299 · Cited by 353
Mali, P., Ye, Z., Hommond, H. H., Yu, X., Lin, J., Chen, G., Zou, J., & Cheng, L. (2008) · Stem Cells · doi:10.1634/stemcells.2008-0346 · Cited by 291
Self-citation
Metadata
- Authors
- Dravid, G., Ye, Z., Hammond, H., Chen, G., Pyle, A., Donovan, P., Yu, X., & Cheng, L.
- Venue
- STEM CELLS
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-11
- Volume
- 23
- Issue
- 10
- Pages
- 1489-1501
- ISSN
- 1066-5099 (ISSN-L)
- 1549-4918
- OpenAlex
- W2156363980
- Cited by
- 342
- References
- 8
- FWCI
- 7.49
- Type
- journal article
- Language
- en
- Open access
- closed
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- Dravid, G., Ye, Z., Hammond, H., Chen, G., Pyle, A., Donovan, P., Yu, X., & Cheng, L. (2005). Defining the Role of Wnt/β‐Catenin Signaling in the Survival, Proliferation, and Self‐Renewal of Human Embryonic Stem Cells. STEM CELLS. https://doi.org/10.1634/stemcells.2005-0034
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