The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Reduced Oct4 Expression Directs a Robust Pluripotent State with Distinct Signaling Activity and Increased Enhancer Occupancy by Oct4 and Nanog
Open accessAbstract
Embryonic stem cell (ESC) pluripotency is governed by a gene regulatory network centered on the transcription factors Oct4 and Nanog. To date, robust self-renewing ESC states have only been obtained through the chemical inhibition of signaling pathways or enforced transgene expression. Here, we show that ESCs with reduced Oct4 expression resulting from heterozygosity also exhibit a stabilized pluripotent state. Despite having reduced Oct4 expression, Oct4(+/-) ESCs show increased genome-wide binding of Oct4, particularly at pluripotency-associated enhancers, homogeneous expression of pluripotency transcription factors, enhanced self-renewal efficiency, and delayed differentiation kinetics. Cells also exhibit increased Wnt expression, enhanced leukemia inhibitory factor (LIF) sensitivity, and reduced responsiveness to fibroblast growth factor. Although they are able to maintain pluripotency in the absence of bone morphogenetic protein, removal of LIF destabilizes pluripotency. Our findings suggest that cells with a reduced Oct4 concentration range are maintained in a robust pluripotent state and that the wild-type Oct4 concentration range enables effective differentiation.
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Cites
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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
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Deconstructing transcriptional heterogeneity in pluripotent stem cells
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A Dynamic Role of TBX3 in the Pluripotency Circuitry
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Metadata
- Authors
- Karwacki-Neisius, V., Göke, J., Osorno, R., Halbritter, F., Ng, J. H., Weiße, A. Y., Wong, F. C. K., Gagliardi, A., Mullin, N. P., Festuccia, N., Colby, D., Tomlinson, S. R., Ng, H.-H., & Chambers, I.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 12
- Issue
- 5
- Pages
- 531-545
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2043399100
- Cited by
- 182
- References
- 7
- FWCI
- 10.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- The paper
- Karwacki-Neisius, V., Göke, J., Osorno, R., Halbritter, F., Ng, J. H., Weiße, A. Y., Wong, F. C. K., Gagliardi, A., Mullin, N. P., Festuccia, N., Colby, D., Tomlinson, S. R., Ng, H.-H., & Chambers, I. (2013). Reduced Oct4 Expression Directs a Robust Pluripotent State with Distinct Signaling Activity and Increased Enhancer Occupancy by Oct4 and Nanog. Cell Stem Cell. https://doi.org/10.1016/j.stem.2013.04.023
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