Otx2 is an intrinsic determinant of the embryonic stem cell state and is required for transition to a stable epiblast stem cell condition - PubMed (original) (raw)
. 2013 Jan 1;140(1):43-55.
doi: 10.1242/dev.085290. Epub 2012 Nov 15.
Affiliations
- PMID: 23154415
- DOI: 10.1242/dev.085290
Otx2 is an intrinsic determinant of the embryonic stem cell state and is required for transition to a stable epiblast stem cell condition
Dario Acampora et al. Development. 2013.
Abstract
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.
Similar articles
- Loss of the Otx2-Binding Site in the Nanog Promoter Affects the Integrity of Embryonic Stem Cell Subtypes and Specification of Inner Cell Mass-Derived Epiblast.
Acampora D, Omodei D, Petrosino G, Garofalo A, Savarese M, Nigro V, Di Giovannantonio LG, Mercadante V, Simeone A. Acampora D, et al. Cell Rep. 2016 Jun 21;15(12):2651-64. doi: 10.1016/j.celrep.2016.05.041. Epub 2016 Jun 9. Cell Rep. 2016. PMID: 27292645 - Hmga2 is necessary for Otx2-dependent exit of embryonic stem cells from the pluripotent ground state.
Navarra A, Musto A, Gargiulo A, Petrosino G, Pierantoni GM, Fusco A, Russo T, Parisi S. Navarra A, et al. BMC Biol. 2016 Mar 31;14:24. doi: 10.1186/s12915-016-0246-5. BMC Biol. 2016. PMID: 27036552 Free PMC article. - Efficient derivation of bovine embryonic stem cells needs more than active core pluripotency factors.
Maruotti J, Muñoz M, Degrelle SA, Gómez E, Louet C, Díez C, de Longchamp PH, Brochard V, Hue I, Caamaño JN, Jouneau A. Maruotti J, et al. Mol Reprod Dev. 2012 Jul;79(7):461-77. doi: 10.1002/mrd.22051. Epub 2012 May 31. Mol Reprod Dev. 2012. PMID: 22573702 - Regulatory role of Klf5 in early mouse development and in embryonic stem cells.
Parisi S, Russo T. Parisi S, et al. Vitam Horm. 2011;87:381-97. doi: 10.1016/B978-0-12-386015-6.00037-8. Vitam Horm. 2011. PMID: 22127252 Review. - Epiblast stem cells contribute new insight into pluripotency and gastrulation.
Chenoweth JG, McKay RD, Tesar PJ. Chenoweth JG, et al. Dev Growth Differ. 2010 Apr;52(3):293-301. doi: 10.1111/j.1440-169X.2010.01171.x. Epub 2010 Mar 7. Dev Growth Differ. 2010. PMID: 20298258 Review.
Cited by
- Large-scale analysis of the integration of enhancer-enhancer signals by promoters.
Martinez-Ara M, Comoglio F, van Steensel B. Martinez-Ara M, et al. Elife. 2024 Oct 28;12:RP91994. doi: 10.7554/eLife.91994. Elife. 2024. PMID: 39466837 Free PMC article. - Onco-Ontogeny of Squamous Cell Cancer of the First Pharyngeal Arch Derivatives.
Sat-Muñoz D, Balderas-Peña LM, Gómez-Sánchez E, Martínez-Herrera BE, Trujillo-Hernández B, Quiroga-Morales LA, Salazar-Páramo M, Dávalos-Rodríguez IP, Nuño-Guzmán CM, Velázquez-Flores MC, Ochoa-Plascencia MR, Muciño-Hernández MI, Isiordia-Espinoza MA, Mireles-Ramírez MA, Hernández-Salazar E. Sat-Muñoz D, et al. Int J Mol Sci. 2024 Sep 16;25(18):9979. doi: 10.3390/ijms25189979. Int J Mol Sci. 2024. PMID: 39337467 Free PMC article. Review. - Shared features of blastula and neural crest stem cells evolved at the base of vertebrates.
York JR, Rao A, Huber PB, Schock EN, Montequin A, Rigney S, LaBonne C. York JR, et al. Nat Ecol Evol. 2024 Sep;8(9):1680-1692. doi: 10.1038/s41559-024-02476-8. Epub 2024 Jul 26. Nat Ecol Evol. 2024. PMID: 39060477 Free PMC article. - Transcriptional remodeling by OTX2 directs specification and patterning of mammalian definitive endoderm.
Ee LS, Medina-Cano D, Uyehara CM, Schwarz C, Goetzler E, Salataj E, Polyzos A, Madhuranath S, Evans T, Hadjantonakis AK, Apostolou E, Vierbuchen T, Stadtfeld M. Ee LS, et al. bioRxiv [Preprint]. 2024 May 30:2024.05.30.596630. doi: 10.1101/2024.05.30.596630. bioRxiv. 2024. PMID: 38854146 Free PMC article. Preprint. - Different Types of Pluripotent Stem Cells Represent Different Developmental Stages.
Kondoh H. Kondoh H. Results Probl Cell Differ. 2024;72:11-25. doi: 10.1007/978-3-031-39027-2_2. Results Probl Cell Differ. 2024. PMID: 38509250
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases