The DOI matches its Crossref record; 62 of the 62 references it cites were found in a registry or an index.
Single Mammalian Cells Compensate for Differences in Cellular Volume and DNA Copy Number through Independent Global Transcriptional Mechanisms
Open accessAbstract
Summary Individual mammalian cells exhibit large variability in cellular volume even with the same absolute DNA content and so must compensate for differences in DNA concentration in order to maintain constant concentration of gene expression products. Using single molecule counting and computational image analysis, we show that transcript abundance correlates with cellular volume at the single cell level due to increased global transcription in larger cells. Cell fusion experiments establish that increased cellular content itself can directly increase transcription. Quantitative analysis shows that this mechanism measures the ratio of cellular volume to DNA content, mostly likely through sequestration of a transcriptional factor to DNA. Analysis of transcriptional bursts reveals a separate mechanism for gene dosage compensation after DNA replication that enables proper transcriptional output during early and late S-phase. Our results provide a framework for quantitatively understanding the relationships between DNA content, cell size and gene expression variability in single cells.
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Cites
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Cited by
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Rare cell variability and drug-induced reprogramming as a mode of cancer drug resistance
Shaffer, S. M., Dunagin, M. C., Torborg, S. R., Torre, E. A., Emert, B., Krepler, C., Beqiri, M., Sproesser, K., Brafford, P. A., Xiao, M., et al. (2017) · Nature · doi:10.1038/nature22794 · Cited by 1,218
Self-citationA practical guide to single-cell RNA-sequencing for biomedical research and clinical applications
Haque, A., Engel, J., Teichmann, S. A., & Lönnberg, T. (2017) · Genome Medicine · doi:10.1186/s13073-017-0467-4 · Cited by 1,071
Defining cell types and states with single-cell genomics
Trapnell, C. (2015) · Genome Research · doi:10.1101/gr.190595.115 · Cited by 813
SAVER: gene expression recovery for single-cell RNA sequencing
Huang, M., Wang, J., Torre, E., Dueck, H., Shaffer, S., Bonasio, R., Murray, J. I., Raj, A., Li, M., & Zhang, N. R. (2018) · Nature Methods · doi:10.1038/s41592-018-0033-z · Cited by 747
Self-citation
Metadata
- Authors
- Padovan-Merhar, O., Nair, G. P., Biaesch, A. G., Mayer, A., Scarfone, S., Foley, S. W., Wu, A. R., Churchman, L. S., Singh, A., & Raj, A.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 58
- Issue
- 2
- Pages
- 339-352
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2085020901
- Cited by
- 451
- References
- 62
- FWCI
- 19.30
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Padovan-Merhar, O., Nair, G. P., Biaesch, A. G., Mayer, A., Scarfone, S., Foley, S. W., Wu, A. R., Churchman, L. S., Singh, A., & Raj, A. (2015). Single Mammalian Cells Compensate for Differences in Cellular Volume and DNA Copy Number through Independent Global Transcriptional Mechanisms. Molecular Cell. https://doi.org/10.1016/j.molcel.2015.03.005
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