The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Systems-level dynamic analyses of fate change in murine embryonic stem cells
Open accessAbstract
Molecular regulation of embryonic stem cell (ESC) fate involves a coordinated interaction between epigenetic, transcriptional and translational mechanisms. It is unclear how these different molecular regulatory mechanisms interact to regulate changes in stem cell fate. Here we present a dynamic systems-level study of cell fate change in murine ESCs following a well-defined perturbation. Global changes in histone acetylation, chromatin-bound RNA polymerase II, messenger RNA (mRNA), and nuclear protein levels were measured over 5 days after downregulation of Nanog, a key pluripotency regulator. Our data demonstrate how a single genetic perturbation leads to progressive widespread changes in several molecular regulatory layers, and provide a dynamic view of information flow in the epigenome, transcriptome and proteome. We observe that a large proportion of changes in nuclear protein levels are not accompanied by concordant changes in the expression of corresponding mRNAs, indicating important roles for translational and post-translational regulation of ESC fate. Gene-ontology analysis across different molecular layers indicates that although chromatin reconfiguration is important for altering cell fate, it is preceded by transcription-factor-mediated regulatory events. The temporal order of gene expression alterations shows the order of the regulatory network reconfiguration and offers further insight into the gene regulatory network. Our studies extend the conventional systems biology approach to include many molecular species, regulatory layers and temporal series, and underscore the complexity of the multilayer regulatory mechanisms responsible for changes in protein expression that determine stem cell fate.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Takahashi, K., & Yamanaka, S. (2006) · Cell · doi:10.1016/j.cell.2006.07.024 · Cited by 26,673
Smyth, G. K. (2004) · Statistical Applications in Genetics and Molecular Biology · doi:10.2202/1544-6115.1027 · Cited by 11,829
A bivalent chromatin structure marks key developmental genes in embryonic stem cells
Bernstein, B. E., Mikkelsen, T. S., Xie, X., Kamal, M., Huebert, D. J., Cuff, J., Fry, B., Meissner, A., Wernig, M., Plath, K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.02.041 · Cited by 5,361
Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
Mikkelsen, T. S., Ku, M., Jaffe, D. B., Issac, B., Lieberman, E., Giannoukos, G., Alvarez, P., Brockman, W., Kim, T.-K., Koche, R. P., et al. (2007) · Nature · doi:10.1038/nature06008 · Cited by 4,129
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
Genome-scale DNA methylation maps of pluripotent and differentiated cells
Meissner, A., Mikkelsen, T. S., Gu, H., Wernig, M., Hanna, J., Sivachenko, A., Zhang, X., Bernstein, B. E., Nusbaum, C., Jaffe, D. B., et al. (2008) · Nature · doi:10.1038/nature07107 · Cited by 2,536
A comparison of background correction methods for two-colour microarrays
Ritchie, M. E., Silver, J., Oshlack, A., Holmes, M., Diyagama, D., Holloway, A., & Smyth, G. K. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btm412 · Cited by 907
Sampath, P., Pritchard, D. K., Pabon, L., Reinecke, H., Schwartz, S. M., Morris, D. R., & Murry, C. E. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2008.03.013 · Cited by 277
Research works printed but not linked: 29
- Boyer, L. A. et al. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 441, 349–353 (2006) · DOI
- Boyer, L. A. et al. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122, 947–956 (2005) · DOI · Paper page
- Loh, Y. H. et al. The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nature Genet. 38, 431–440 (2006) · DOI
- Ivanova, N. et al. Dissecting self-renewal in stem cells with RNA interference. Nature 442, 533–538 (2006) · DOI · Paper page
- Kim, J., Chu, J., Shen, X., Wang, J. & Orkin, S. H. An extended transcriptional network for pluripotency of embryonic stem cells. Cell 132, 1049–1061 (2008) · DOI · Paper page
- Chickarmane, V. & Peterson, C. A computational model for understanding stem cell, trophectoderm and endoderm lineage determination. PLoS One 3, e3478 (2008) · DOI
- Chang, W. Y. & Stanford, W. L. Translational control: a new dimension in embryonic stem cell network analysis. Cell Stem Cell 2, 410–412 (2008) · DOI
- Chambers, I. et al. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 113, 643–655 (2003) · DOI · Paper page
- Mitsui, K. et al. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 113, 631–642 (2003) · DOI · Paper page
- Chambers, I. et al. Nanog safeguards pluripotency and mediates germline development. Nature 450, 1230–1234 (2007) · DOI · Paper page
- Unwin, R. D. et al. Quantitative proteomics reveals posttranslational control as a regulatory factor in primary hematopoietic stem cells. Blood 107, 4687–4694 (2006) · DOI
- Spooncer, E. et al. Developmental fate determination and marker discovery in hematopoietic stem cell biology using proteomic fingerprinting. Mol. Cell. Proteomics 7, 573–581 (2008) · DOI
- van den Berg, D. L. et al. Estrogen-related receptor β interacts with Oct4 to positively regulate Nanog gene expression. Mol. Cell. Biol. 28, 5986–5995 (2008) · DOI
- Tay, Y., Zhang, J., Thomson, A. M., Lim, B. & Rigoutsos, I. MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation. Nature 455, 1124–1128 (2008) · DOI
- Marson, A. et al. Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells. Cell 134, 521–533 (2008) · DOI · Paper page
- Bonifer, C., Hoogenkamp, M., Krysinska, H. & Tagoh, H. How transcription factors program chromatin—lessons from studies of the regulation of myeloid-specific genes. Semin. Immunol. 20, 257–263 (2008) · DOI · Paper page
- Okita, K., Ichisaka, T. & Yamanaka, S. Generation of germline-competent induced pluripotent stem cells. Nature 448, 313–317 (2007) · DOI · Paper page
- Wang, J. et al. A protein interaction network for pluripotency of embryonic stem cells. Nature 444, 364–368 (2006) · DOI · Paper page
- Macarthur, B. D., Ma’ayan, A. & Lemischka, I. R. Systems biology of stem cell fate and cellular reprogramming. Nature Rev. Mol. Cell Biol. 10, 672–681 (2009) · DOI
- Graf, T. & Stadtfeld, M. Heterogeneity of embryonic and adult stem cells. Cell Stem Cell 3, 480–483 (2008) · DOI · Paper page
- Dietrich, J. E. & Hiiragi, T. Stochastic patterning in the mouse pre-implantation embryo. Development 134, 4219–4231 (2007) · DOI · Paper page
- Singh, A. M., Hamazaki, T., Hankowski, K. E. & Terada, N. A heterogeneous expression pattern for Nanog in embryonic stem cells. Stem Cells 25, 2534–2542 (2007) · DOI
- Kalmar, T. et al. Regulated fluctuations in Nanog expression mediate cell fate decisions in embryonic stem cells. PLoS Biol. 7, e1000149 (2009) · DOI · Paper page
- Airoldi, E. M. Getting started in probabilistic graphical models. PLOS Comput. Biol. 3, e252 (2007) · DOI
- Liu, C. L., Schreiber, S. L. & Bernstein, B. E. Development and validation of a T7 based linear amplification for genomic DNA. BMC Genomics 4, 19 (2003) · DOI
- Kislinger, T. et al. Global survey of organ and organelle protein expression in mouse: combined proteomic and transcriptomic profiling. Cell 125, 173–186 (2006) · DOI · Paper page
- Yang, Y. H. et al. Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation. Nucleic Acids Res. 30, e15 (2002) · DOI
- Benjamini, Y., Drai, D., Elmer, G., Kafkafi, N. & Golani, I. Controlling the false discovery rate in behavior genetics research. Behav. Brain Res. 125, 279–284 (2001) · DOI · Paper page
- Eichler, G. S., Huang, S. & Ingber, D. E. Gene Expression Dynamics Inspector (GEDI): for integrative analysis of expression profiles. Bioinformatics 19, 2321–2322 (2003) · DOI
Cited by
Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566
On the Dependency of Cellular Protein Levels on mRNA Abundance
Liu, Y., Beyer, A., & Aebersold, R. (2016) · Cell · doi:10.1016/j.cell.2016.03.014 · Cited by 3,221
McAlister, G. C., Nusinow, D. P., Jedrychowski, M. P., Wühr, M., Huttlin, E. L., Erickson, B. K., Rad, R., Haas, W., & Gygi, S. P. (2014) · Analytical Chemistry · doi:10.1021/ac502040v · Cited by 1,263
Densely Interconnected Transcriptional Circuits Control Cell States in Human Hematopoiesis
Novershtern, N., Subramanian, A., Lawton, L. N., Mak, R. H., Haining, W. N., McConkey, M. E., Habib, N., Yosef, N., Chang, C. Y., Shay, T., et al. (2011) · Cell · doi:10.1016/j.cell.2011.01.004 · Cited by 942
Defining an essential transcription factor program for naïve pluripotency
Dunn, S.-J., Martello, G., Yordanov, B., Emmott, S., & Smith, A. G. (2014) · Science · doi:10.1126/science.1248882 · Cited by 370
Metadata
- Authors
- Lu, R., Markowetz, F., Unwin, R. D., Leek, J. T., Airoldi, E. M., MacArthur, B. D., Lachmann, A., Rozov, R., Ma’ayan, A., Boyer, L. A., Troyanskaya, O. G., Whetton, A. D., & Lemischka, I. R.
- Venue
- Nature
- Published
- 2009-11-19
- Volume
- 462
- Issue
- 7271
- Pages
- 358-362
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2124486107
- Cited by
- 296
- References
- 8
- FWCI
- 12.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- Licence
- www.springer.com/tdm (tdm)
- www.springer.com/tdm (vor)
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
