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The Cell-Cycle State of Stem Cells Determines Cell Fate Propensity
Open accessAbstract
Self-renewal and differentiation of stem cells are fundamentally associated with cell-cycle progression to enable tissue specification, organ homeostasis, and potentially tumorigenesis. However, technical challenges have impaired the study of the molecular interactions coordinating cell fate choice and cell-cycle progression. Here, we bypass these limitations by using the FUCCI reporter system in human pluripotent stem cells and show that their capacity of differentiation varies during the progression of their cell cycle. These mechanisms are governed by the cell-cycle regulators cyclin D1-3 that control differentiation signals such as the TGF-β-Smad2/3 pathway. Conversely, cell-cycle manipulation using a small molecule directs differentiation of hPSCs and provides an approach to generate cell types with a clinical interest. Our results demonstrate that cell fate decisions are tightly associated with the cell-cycle machinery and reveal insights in the mechanisms synchronizing differentiation and proliferation in developing tissues.
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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
Coexistence of Quiescent and Active Adult Stem Cells in Mammals
Li, L., & Clevers, H. (2010) · Science · doi:10.1126/science.1180794 · Cited by 1,247
Fry, D. W., Harvey, P. J., Keller, P. R., Elliott, W. L., Meade, M., Trachet, E., Albassam, M., Zheng, X., Leopold, W. R., Pryer, N. K., et al. (2004) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.1427.3.11 · Cited by 1,236
Mouse development and cell proliferation in the absence of D-cyclins
Kozar, K., Ciemerych, M. A., Rebel, V. I., Shigematsu, H., Zagozdzon, A., Sicinska, E., Geng, Y., Yu, Q., Bhattacharya, S., Bronson, R. T., et al. (2004) · Cell · doi:10.1016/j.cell.2004.07.025 · Cited by 647
The tortoise and the hair: slow-cycling cells in the stem cell race
Fuchs, E. (2009) · Cell · doi:10.1016/j.cell.2009.05.002 · Cited by 371
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Kowalczyk, M. S., Tirosh, I., Heckl, D., Rao, T. N., Dixit, A., Haas, B. J., Schneider, R. K., Wagers, A. J., Ebert, B. L., & Regev, A. (2015) · Genome Research · doi:10.1101/gr.192237.115 · Cited by 778
Chu, L.-F., Leng, N., Zhang, J., Hou, Z., Mamott, D., Vereide, D. T., Choi, J., Kendziorski, C., Stewart, R., & Thomson, J. A. (2016) · Genome Biology · doi:10.1186/s13059-016-1033-x · Cited by 477
Neurogenesis in the embryonic and adult brain: same regulators, different roles
Urbán, N., & Guillemot, F. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00396 · Cited by 493
Fundamental limits on dynamic inference from single-cell snapshots
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Metadata
- Authors
- Pauklin, S., & Vallier, L.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 155
- Issue
- 1
- Pages
- 135-147
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2122986552
- Cited by
- 623
- References
- 5
- FWCI
- 21.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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