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Oct4 kinetics predict cell lineage patterning in the early mammalian embryo

Plachta, Nicolas and Bollenbach, Tobias and Pease, Shirley and Fraser, Scott E. and Pantazis, Periklis (2011) Oct4 kinetics predict cell lineage patterning in the early mammalian embryo. Nature Cell Biology, 13 (2). pp. 117-123. ISSN 1465-7392.

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Transcription factors are central to sustaining pluripotency, yet little is known about transcription factor dynamics in defining pluripotency in the early mammalian embryo. Here, we establish a fluorescence decay after photoactivation (FDAP) assay to quantitatively study the kinetic behaviour of Oct4, a key transcription factor controlling pre-implantation development in the mouse embryo. FDAP measurements reveal that each cell in a developing embryo shows one of two distinct Oct4 kinetics, before there are any morphologically distinguishable differences or outward signs of lineage patterning. The differences revealed by FDAP are due to differences in the accessibility of Oct4 to its DNA binding sites in the nucleus. Lineage tracing of the cells in the two distinct sub-populations demonstrates that the Oct4 kinetics predict lineages of the early embryo. Cells with slower Oct4 kinetics are more likely to give rise to the pluripotent cell lineage that contributes to the inner cell mass. Those with faster Oct4 kinetics contribute mostly to the extra-embryonic lineage. Our findings identify Oct4 kinetics, rather than differences in total transcription factor expression levels, as a predictive measure of developmental cell lineage patterning in the early mouse embryo.

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Plachta, Nicolas0000-0002-5035-7425
Bollenbach, Tobias0000-0003-4398-476X
Fraser, Scott E.0000-0002-5377-0223
Pantazis, Periklis0000-0002-8367-9332
Additional Information:© 2011 Macmillan Publishers Limited. Received 09 September 2010; Accepted 07 November 2010; Published online 23 January 2011; Corrected online 28 January 2011. In the version of this article initially published online and in print, the values for k_(out) and k_(in) in table 1 were incorrect. The correct values are (×10^(−3)s^(−1)). This error has been corrected in both the HTML and PDF versions of the article. We especially thank Juan Silva and John Earle for excellent technical support with mouse embryo work. We also thank H. Schöler, J. Lippincott-Schwartz, G. Patterson and Li-Jin Chew for constructs. N.P. is supported by California Institute for Regenerative Medicine (CIRM), European Molecular Biology Organization (EMBO) and Swiss National Science Foundation (SNF), fellowships. T.B. was supported by the Alexander von Humboldt foundation. P.P. is supported by the German Science Foundation (DFG). This work was supported by the Beckman Institute and Biological Imaging Center at the California Institute of Technology and by the NHGRI Center of Excellence in Genomic Science grant P50HG004071. Author Contributions: T.B. performed the quantitative analysis. S.P. performed microinjections into mouse embryos. N.P., S.E.F. and P.P. designed and N.P. and P.P. carried out all other experiments.
Funding AgencyGrant Number
California Institute for Regenerative Medicine (CIRM)UNSPECIFIED
European Molecular Biology Organization (EMBO)UNSPECIFIED
Swiss National Science Foundation (SNSF)UNSPECIFIED
Alexander von Humboldt FoundationUNSPECIFIED
Deutsche Forschungsgemeinschaft (DFG)UNSPECIFIED
Caltech Beckman InstituteUNSPECIFIED
Issue or Number:2
Record Number:CaltechAUTHORS:20110315-131327456
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:22901
Deposited By: Tony Diaz
Deposited On:15 Mar 2011 21:05
Last Modified:03 Oct 2019 02:41

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