Adam Burton1,6, Julius Muller2,6, Shengjiang Tu4, Pablo Padilla-Longoria3, Ernesto Guccione2,5,* and Maria-Elena Torres-Padilla1,*
1 Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM U964, Universite de Strasbourg, F-67404 Illkirch, CU de Strasbourg, France
2 Division of Cancer Genetics and Therapeutics, Laboratory of Chromatin, Epigenetics and Differentiation, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673, Singapore
3 Instituto de Investigaciones en Matematicas Aplicadas y en Sistemas, Universidad Nacional Autonoma de Mexico, C.U., Distrito Federal 04510, Mexico
4 Howard Hughes Medical Institute, Department of Biochemistry, New York University School of Medicine, 522 First Avenue, New York, NY 10016, USA
5 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
6 These authors contributed equally to this work
Published in Cell Reports on 31 October 2013.
Cell plasticity or potency is necessary for the formation of multiple cell types. The mechanisms underlying this plasticity are largely unknown. Preimplantation mouse embryos undergo drastic changes in cellular potency, starting with the totipotent zygote through to the formation of the pluripotent inner cell mass (ICM) and differentiated trophectoderm in the blastocyst. Here, we set out to identify and functionally characterize chromatin modifiers that define the transitions of potency and cell fate in the mouse embryo. Using a quantitative microfluidics approach in single cells, we show that developmental transitions are marked by distinctive combinatorial profiles of epigenetic modifiers. Pluripotent cells of the ICM are distinct from their differentiated trophectoderm counterparts. We show that PRDM14 is heterogeneously expressed in 4-cell-stage embryos. Forced expression of PRDM14 at the 2-cell stage leads to increased H3R26me2 and can induce a pluripotent ICM fate. Our results shed light on the epigenetic networks that govern cellular potency and identity in vivo.
Figure Legend: Expression levels of 35 chromatin modifiers in single cells derived from embryos at all stages, from oocyte to blastocyst, were subjected to hierarchical clustering. Important clusters and trends were identified and visualized by Principal Component Analysis (PCA) and a semiquantitative epigenetic landscape was computed from the mean values (centers of gravity) and SDs (spread) of the individual cells for each developmental stage in the PCA.
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