The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Endogenous Wnt signalling in human embryonic stem cells generates an equilibrium of distinct lineage-specified progenitors
Open accessAbstract
The pluripotent nature of human embryonic stem cells (hESCs) makes them convenient for deriving therapeutically relevant cells. Here we show using Wnt reporter hESC lines that the cells are heterogeneous with respect to endogenous Wnt signalling activity. Moreover, the level of Wnt signalling activity in individual cells correlates with differences in clonogenic potential and lineage-specific differentiation propensity. The addition of Wnt protein or, conversely, a small-molecule Wnt inhibitor (IWP2) reduces heterogeneity, allowing stable expansion of Wnthigh or Wntlow hESC populations, respectively. On differentiation, the Wnthigh hESCs predominantly form endodermal and cardiac cells, whereas the Wntlow hESCs generate primarily neuroectodermal cells. Thus, heterogeneity with respect to endogenous Wnt signalling underlies much of the inefficiency in directing hESCs towards specific cell types. The relatively uniform differentiation potential of the Wnthigh and Wntlow hESCs leads to faster and more efficient derivation of targeted cell types from these populations. Human embryonic stem cell cultures are morphologically heterogeneous. Here, differences in Wnt signalling are shown to contribute to this heterogeneity, cells containing high levels of Wnt form endodermal and cardiac cells, whereas cells with low Wnt form neuroectodermal cells, when differentiation is induced.
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Cites
Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling
Chambers, S. M., Fasano, C. A., Papapetrou, E. P., Tomishima, M., Sadelain, M., & Studer, L. (2009) · Nature Biotechnology · doi:10.1038/nbt.1529 · Cited by 3,620
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
Self-citationA ROCK inhibitor permits survival of dissociated human embryonic stem cells
Watanabe, K., Ueno, M., Kamiya, D., Nishiyama, A., Matsumura, M., Wataya, T., Takahashi, J. B., Nishikawa, S., Nishikawa, S.-I., Muguruma, K., et al. (2007) · Nature Biotechnology · doi:10.1038/nbt1310 · Cited by 2,055
Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population
Yang, L., Soonpaa, M. H., Adler, E. D., Roepke, T. K., Kattman, S. J., Kennedy, M., Henckaerts, E., Bonham, K., Abbott, G. W., Linden, R. M., et al. (2008) · Nature · doi:10.1038/nature06894 · Cited by 1,389
Making a commitment: cell lineage allocation and axis patterning in the early mouse embryo
Arnold, S. J., & Robertson, E. J. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2618 · Cited by 816
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Warmflash, A., Sorre, B., Etoc, F., Siggia, E. D., & Brivanlou, A. H. (2014) · Nature Methods · doi:10.1038/nmeth.3016 · Cited by 885
Efficient generation of lung and airway epithelial cells from human pluripotent stem cells
Huang, S. X. L., Islam, M. N., O'Neill, J., Hu, Z., Yang, Y.-G., Chen, Y.-W., Mumau, M., Green, M. D., Vunjak-Novakovic, G., Bhattacharya, J., et al. (2014) · Nature Biotechnology · doi:10.1038/nbt.2754 · Cited by 567
Loh, K. M., Ang, L. T., Zhang, J., Kumar, V., Ang, J., Auyeong, J. Q., Lee, K. L., Choo, S. H., Lim, C. Y. Y., Nichane, M., et al. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2013.12.007 · Cited by 418
Self-citationOrigin and differentiation of vascular smooth muscle cells
Wang, G., Jacquet, L., Karamariti, E., & Xu, Q. (2015) · The Journal of Physiology · doi:10.1113/jp270033 · Cited by 299
A Modular Platform for Differentiation of Human PSCs into All Major Ectodermal Lineages
Tchieu, J., Zimmer, B., Fattahi, F., Amin, S., Zeltner, N., Chen, S., & Studer, L. (2017) · Cell Stem Cell · doi:10.1016/j.stem.2017.08.015 · Cited by 235
Metadata
- Authors
- Blauwkamp, T. A., Nigam, S., Ardehali, R., Weissman, I. L., & Nusse, R.
- Venue
- Nature Communications
- Published
- 2012-09-18
- Volume
- 3
- Issue
- 1
- Pages
- 1070-1070
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2018744859
- Cited by
- 184
- References
- 5
- FWCI
- 7.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
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