The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Exit from Pluripotency Is Gated by Intracellular Redistribution of the bHLH Transcription Factor Tfe3
Open accessAbstract
Factors that sustain self-renewal of mouse embryonic stem cells (ESCs) are well described. In contrast, the machinery regulating exit from pluripotency is ill defined. In a large-scale small interfering RNA (siRNA) screen, we found that knockdown of the tumor suppressors Folliculin (Flcn) and Tsc2 prevent ESC commitment. Tsc2 lies upstream of mammalian target of rapamycin (mTOR), whereas Flcn acts downstream and in parallel. Flcn with its interaction partners Fnip1 and Fnip2 drives differentiation by restricting nuclear localization and activity of the bHLH transcription factor Tfe3. Conversely, enforced nuclear Tfe3 enables ESCs to withstand differentiation conditions. Genome-wide location and functional analyses showed that Tfe3 directly integrates into the pluripotency circuitry through transcriptional regulation of Esrrb. These findings identify a cell-intrinsic rheostat for destabilizing ground-state pluripotency to allow lineage commitment. Congruently, stage-specific subcellular relocalization of Tfe3 suggests that Flcn-Fnip1/2 contributes to developmental progression of the pluripotent epiblast in vivo.
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Cites
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
Self-citationConversion of embryonic stem cells into neuroectodermal precursors in adherent monoculture
Ying, Q.-L., Stavridis, M., Griffiths, D., Li, M., & Smith, A. (2003) · Nature Biotechnology · doi:10.1038/nbt780 · Cited by 1,504
Self-citationA parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells
Niwa, H., Ogawa, K., Shimosato, D., & Adachi, K. (2009) · Nature · doi:10.1038/nature08113 · Cited by 872
Cited by
Lysosomes as dynamic regulators of cell and organismal homeostasis
Ballabio, A., & Bonifacino, J. S. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0185-4 · Cited by 1,469
Dynamic stem cell states: Naive to primed pluripotency in rodents and humans
Weinberger, L., Ayyash, M., Novershtern, N., & Hanna, J. H. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2015.28 · Cited by 622
Reorganization of enhancer patterns in transition from naive to primed pluripotency
Buecker, C., Srinivasan, R., Wu, Z., Calo, E., Acampora, D., Faial, T., Simeone, A., Tan, M., Swigut, T., & Wysocka, J. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.04.003 · Cited by 507
Formative pluripotency: the executive phase in a developmental continuum
Smith, A. (2017) · Development · doi:10.1242/dev.142679 · Cited by 474
Self-citationTFEB and TFE3: Linking Lysosomes to Cellular Adaptation to Stress
Raben, N., & Puertollano, R. (2016) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-111315-125407 · Cited by 437
Metadata
- Authors
- Betschinger, J., Nichols, J., Dietmann, S., Corrin, P. D., Paddison, P. J., & Smith, A.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 153
- Issue
- 2
- Pages
- 335-347
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2138035159
- Cited by
- 342
- References
- 3
- FWCI
- 12.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Betschinger, J., Nichols, J., Dietmann, S., Corrin, P. D., Paddison, P. J., & Smith, A. (2013). Exit from Pluripotency Is Gated by Intracellular Redistribution of the bHLH Transcription Factor Tfe3. Cell. https://doi.org/10.1016/j.cell.2013.03.012
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