The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.
Dynamic Heterogeneity and DNA Methylation in Embryonic Stem Cells
Open accessAbstract
Cell populations can be strikingly heterogeneous, composed of multiple cellular states, each exhibiting stochastic noise in its gene expression. A major challenge is to disentangle these two types of variability and to understand the dynamic processes and mechanisms that control them. Embryonic stem cells (ESCs) provide an ideal model system to address this issue because they exhibit heterogeneous and dynamic expression of functionally important regulatory factors. We analyzed gene expression in individual ESCs using single-molecule RNA-FISH and quantitative time-lapse movies. These data discriminated stochastic switching between two coherent (correlated) gene expression states and burst-like transcriptional noise. We further showed that the "2i" signaling pathway inhibitors modulate both types of variation. Finally, we found that DNA methylation plays a key role in maintaining these metastable states. Together, these results show how ESC gene expression states and dynamics arise from a combination of intrinsic noise, coherent cellular states, and epigenetic regulation.
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BackgroundSelf-citation
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
Single-cell chromatin accessibility reveals principles of regulatory variation
Buenrostro, J. D., Wu, B., Litzenburger, U. M., Ruff, D., Gonzales, M. L., Snyder, M. P., Chang, H. Y., & Greenleaf, W. J. (2015) · Nature · doi:10.1038/nature14590 · Cited by 2,308
Function and information content of DNA methylation
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Single-cell ChIP-seq reveals cell subpopulations defined by chromatin state
Rotem, A., Ram, O., Shoresh, N., Sperling, R. A., Goren, A., Weitz, D. A., & Bernstein, B. E. (2015) · Nature Biotechnology · doi:10.1038/nbt.3383 · Cited by 854
Epigenetic modulators, modifiers and mediators in cancer aetiology and progression
Feinberg, A. P., Koldobskiy, M. A., & Göndör, A. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.13 · Cited by 841
Metadata
- Authors
- Singer, Z. S., Yong, J., Tischler, J., Hackett, J. A., Altinok, A., Surani, M. A., Cai, L., & Elowitz, M. B.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 55
- Issue
- 2
- Pages
- 319-331
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2068751516
- Cited by
- 279
- References
- 20
- FWCI
- 13.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Singer, Z. S., Yong, J., Tischler, J., Hackett, J. A., Altinok, A., Surani, M. A., Cai, L., & Elowitz, M. B. (2014). Dynamic Heterogeneity and DNA Methylation in Embryonic Stem Cells. Molecular Cell. https://doi.org/10.1016/j.molcel.2014.06.029
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