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Systematic Identification of Culture Conditions for Induction and Maintenance of Naive Human Pluripotency
Open accessAbstract
Embryonic stem cells (ESCs) of mice and humans have distinct molecular and biological characteristics, raising the question of whether an earlier, "naive" state of pluripotency may exist in humans. Here we took a systematic approach to identify small molecules that support self-renewal of naive human ESCs based on maintenance of endogenous OCT4 distal enhancer activity, a molecular signature of ground state pluripotency. Iterative chemical screening identified a combination of five kinase inhibitors that induces and maintains OCT4 distal enhancer activity when applied directly to conventional human ESCs. These inhibitors generate human pluripotent cells in which transcription factors associated with the ground state of pluripotency are highly upregulated and bivalent chromatin domains are depleted. Comparison with previously reported naive human ESCs indicates that our conditions capture a distinct pluripotent state in humans that closely resembles that of mouse ESCs. This study presents a framework for defining the culture requirements of naive human pluripotent cells.
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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
Revisiting Global Gene Expression Analysis
Lovén, J., Orlando, D. A., Sigova, A. A., Lin, C. Y., Rahl, P. B., Burge, C. B., Levens, D. L., Lee, T. I., & Young, R. A. (2012) · Cell · doi:10.1016/j.cell.2012.10.012 · Cited by 616
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Human organoids: model systems for human biology and medicine
Kim, J., Koo, B.-K., & Knoblich, J. A. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0259-3 · Cited by 2,187
TGF-β and the TGF-β family: context-dependent roles in cell and tissue physiology
Morikawa, M., Derynck, R., & Miyazono, K. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a021873 · Cited by 1,321
Stretch-activated ion channel Piezo1 directs lineage choice in human neural stem cells
Pathak, M. M., Nourse, J. L., Tran, T., Hwe, J., Arulmoli, J., Le, D. T. T., Bernardis, E., Flanagan, L. A., & Tombola, F. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1409802111 · Cited by 657
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
Induced Pluripotent Stem Cells Meet Genome Editing
Hockemeyer, D., & Jaenisch, R. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.04.013 · Cited by 499
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Metadata
- Authors
- Theunissen, T. W., Powell, B. E., Wang, H., Mitalipova, M., Faddah, D. A., Reddy, J., Fan, Z. P., Maetzel, D., Ganz, K., Shi, L., Lungjangwa, T., Imsoonthornruksa, S., Stelzer, Y., Rangarajan, S., D’Alessio, A., Zhang, J., Gao, Q., Dawlaty, M. M., Young, R. A., Gray, N. S., & Jaenisch, R.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2014-10
- Volume
- 15
- Issue
- 4
- Pages
- 471-487
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2093822374
- Cited by
- 888
- References
- 2
- FWCI
- 34.80
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Theunissen, T. W., Powell, B. E., Wang, H., Mitalipova, M., Faddah, D. A., Reddy, J., Fan, Z. P., Maetzel, D., Ganz, K., Shi, L., Lungjangwa, T., Imsoonthornruksa, S., Stelzer, Y., Rangarajan, S., D’Alessio, A., Zhang, J., Gao, Q., Dawlaty, M. M., Young, R. A., . . . Jaenisch, R. (2014). Systematic Identification of Culture Conditions for Induction and Maintenance of Naive Human Pluripotency. Cell Stem Cell. https://doi.org/10.1016/j.stem.2014.07.002
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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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