The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Regulated Fluctuations in Nanog Expression Mediate Cell Fate Decisions in Embryonic Stem Cells
Open accessAbstract
There is evidence that pluripotency of mouse embryonic stem (ES) cells is associated with the activity of a network of transcription factors with Sox2, Oct4, and Nanog at the core. Using fluorescent reporters for the expression of Nanog, we observed that a population of ES cells is best described by a dynamic distribution of Nanog expression characterized by two peaks defined by high (HN) and low (LN) Nanog expression. Typically, the LN state is 5%-20% of the total population, depending on the culture conditions. Modelling of the activity of Nanog reveals that a simple network of Oct4/Sox2 and Nanog activity can account for the observed distribution and its properties as long as the transcriptional activity is tuned by transcriptional noise. The model also predicts that the LN state is unstable, something that is born out experimentally. While in this state, cells can differentiate. We suggest that transcriptional fluctuations in Nanog expression are an essential element of the pluripotent state and that the function of Sox2, Oct4, and Nanog is to act as a network that promotes and maintains transcriptional noise to interfere with the differentiation signals.
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Cites
Takahashi, K., & Yamanaka, S. (2006) · Cell · doi:10.1016/j.cell.2006.07.024 · Cited by 26,673
A bivalent chromatin structure marks key developmental genes in embryonic stem cells
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The ground state of embryonic stem cell self-renewal
Ying, Q.-L., Wray, J., Nichols, J., Batlle-Morera, L., Doble, B., Woodgett, J., Cohen, P., & Smith, A. (2008) · Nature · doi:10.1038/nature06968 · Cited by 3,442
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Cited by
Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells
Klein, A. M., Mazutis, L., Akartuna, I., Tallapragada, N., Veres, A., Li, V., Peshkin, L., Weitz, D. A., & Kirschner, M. W. (2015) · Cell · doi:10.1016/j.cell.2015.04.044 · Cited by 3,356
Parallel single-cell sequencing links transcriptional and epigenetic heterogeneity
Angermueller, C., Clark, S. J., Lee, H. J., Macaulay, I. C., Teng, M. J., Hu, T. X., Krueger, F., Smallwood, S. A., Ponting, C. P., Voet, T., et al. (2016) · Nature Methods · doi:10.1038/nmeth.3728 · Cited by 717
Single Cell RNA-Sequencing of Pluripotent States Unlocks Modular Transcriptional Variation
Kolodziejczyk, A. A., Kim, J. K., Tsang, J. C. H., Ilicic, T., Henriksson, J., Natarajan, K. N., Tuck, A. C., Gao, X., Bühler, M., Liu, P., et al. (2015) · Cell Stem Cell · doi:10.1016/j.stem.2015.09.011 · Cited by 570
Sasagawa, Y., Nikaido, I., Hayashi, T., Danno, H., Uno, K. D., Imai, T., & Ueda, H. R. (2013) · Genome Biology · doi:10.1186/gb-2013-14-4-r31 · Cited by 455
Deconstructing transcriptional heterogeneity in pluripotent stem cells
Kumar, R. M., Cahan, P., Shalek, A. K., Satija, R., Jay DaleyKeyser, A., Li, H., Zhang, J., Pardee, K., Gennert, D., Trombetta, J. J., et al. (2014) · Nature · doi:10.1038/nature13920 · Cited by 356
Metadata
- Authors
- Kalmar, T., Lim, C., Hayward, P., Muñoz-Descalzo, S., Nichols, J., Garcia-Ojalvo, J., & Martinez Arias, A.
- Venue
- PLoS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-07-07
- Volume
- 7
- Issue
- 7
- Pages
- e1000149
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- OpenAlex
- W2142806844
- Cited by
- 558
- References
- 5
- FWCI
- 17.52
- Type
- journal article
- Language
- en
- Open access
- gold
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