The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Otx2 is an intrinsic determinant of the embryonic stem cell state and is required for transition to a stable epiblast stem cell condition
Open accessAbstract
Mouse embryonic stem cells (ESCs) represent the naïve ground state of the preimplantation epiblast and epiblast stem cells (EpiSCs) represent the primed state of the postimplantation epiblast. Studies have revealed that the ESC state is maintained by a dynamic mechanism characterized by cell-to-cell spontaneous and reversible differences in sensitivity to self-renewal and susceptibility to differentiation. This metastable condition ensures indefinite self-renewal and, at the same time, predisposes ESCs for differentiation to EpiSCs. Despite considerable advances, the molecular mechanism controlling the ESC state and pluripotency transition from ESCs to EpiSCs have not been fully elucidated. Here we show that Otx2, a transcription factor essential for brain development, plays a crucial role in ESCs and EpiSCs. Otx2 is required to maintain the ESC metastable state by antagonizing ground state pluripotency and promoting commitment to differentiation. Furthermore, Otx2 is required for ESC transition into EpiSCs and, subsequently, to stabilize the EpiSC state by suppressing, in pluripotent cells, the mesendoderm-to-neural fate switch in cooperation with BMP4 and Fgf2. However, according to its central role in neural development and differentiation, Otx2 is crucially required for the specification of ESC-derived neural precursors fated to generate telencephalic and mesencephalic neurons. We propose that Otx2 is a novel intrinsic determinant controlling the functional integrity of ESCs and EpiSCs.
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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
Conversion 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
A 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
Reynolds, N., Latos, P., Hynes-Allen, A., Loos, R., Leaford, D., O'Shaughnessy, A., Mosaku, O., Signolet, J., Brennecke, P., Kalkan, T., et al. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2012.02.020 · Cited by 236 · cited 1×
“, 2007) or abnormal expression of NuRD complex components (Reynolds et al., 2012; Kaji et al., 2006), the expression of Fgf4, Fgfr1-4, Mbd3, Mta1 and Mta2, Rbap46 (Rbbp7 – Mouse Genome Informatics) and Hdac1 was analyzed, and showed a very mild reduction in Otx2−/− ESCs only for Fgf4 (supplementary material Fig.”
BackgroundDi Salvio, M., Di Giovannantonio, L. G., Acampora, D., Prosperi, R., Omodei, D., Prakash, N., Wurst, W., & Simeone, A. (2010) · Nature Neuroscience · doi:10.1038/nn.2661 · Cited by 118
Cited by
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
Self-citationFormative pluripotency: the executive phase in a developmental continuum
Smith, A. (2017) · Development · doi:10.1242/dev.142679 · Cited by 474
Epigenetic reprogramming in mice and humans: From fertilization to primordial germ cell development
Singh, A., Rappolee, D. A., & Ruden, D. M. (2023) · Cells · doi:10.3390/cells12141874 · Cited by 50
Athanasouli, P., Balli, M., De Jaime-Soguero, A., Boel, A., Papanikolaou, S., van der Veer, B. K., Janiszewski, A., Vanhessche, T., Francis, A., El Laithy, Y., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36914-1 · Cited by 31
Brinkhof, B., van Tol, H. T., Groot Koerkamp, M. J., Riemers, F. M., IJzer, S. G., Mashayekhi, K., Haagsman, H. P., & Roelen, B. A. (2015) · BMC Genomics · doi:10.1186/s12864-015-1448-x · Cited by 26
Metadata
- Authors
- Acampora, D., Di Giovannantonio, L. G., & Simeone, A.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2013-01-01
- Volume
- 140
- Issue
- 1
- Pages
- 43-55
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2166131563
- Cited by
- 194
- References
- 5
- FWCI
- 4.30
- Type
- journal article
- Language
- en
- Open access
- green
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