A program of successive gene expression in mouse one-cell embryos
Maki Asami,
Brian Y.H. Lam,
Martin Hoffmann,
Toru Suzuki,
Xin Lu,
Naoko Yoshida,
Marcella K. Ma,
Kara Rainbow,
Miodrag Gužvić,
Matthew D. VerMilyea,
Giles S.H. Yeo,
Christoph A. Klein,
Anthony C.F. Perry
Affiliations
Maki Asami
Laboratory of Mammalian Molecular Embryology, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
Brian Y.H. Lam
Medical Research Council (MRC) Metabolic Diseases Unit, Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories, Addenbrooke’s Hospital, University of Cambridge, Cambridge CB2 0QQ, UK
Martin Hoffmann
Project Group Personalized Tumor Therapy, Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Regensburg, Germany
Toru Suzuki
Laboratory of Mammalian Molecular Embryology, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
Xin Lu
Experimental Medicine and Therapy Research, University of Regensburg, Regensburg, Germany
Naoko Yoshida
Department of Pathology, Kansai Medical University, Osaka 573-1010, Japan
Marcella K. Ma
Medical Research Council (MRC) Metabolic Diseases Unit, Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories, Addenbrooke’s Hospital, University of Cambridge, Cambridge CB2 0QQ, UK
Kara Rainbow
Medical Research Council (MRC) Metabolic Diseases Unit, Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories, Addenbrooke’s Hospital, University of Cambridge, Cambridge CB2 0QQ, UK
Miodrag Gužvić
Experimental Medicine and Therapy Research, University of Regensburg, Regensburg, Germany
Matthew D. VerMilyea
Embryology and Andrology Laboratories, Ovation Fertility Austin, Austin, TX 78731, USA
Giles S.H. Yeo
Medical Research Council (MRC) Metabolic Diseases Unit, Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories, Addenbrooke’s Hospital, University of Cambridge, Cambridge CB2 0QQ, UK; Corresponding author
Christoph A. Klein
Project Group Personalized Tumor Therapy, Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Regensburg, Germany; Experimental Medicine and Therapy Research, University of Regensburg, Regensburg, Germany; Corresponding author
Anthony C.F. Perry
Laboratory of Mammalian Molecular Embryology, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK; Corresponding author
Summary: At the moment of union in fertilization, sperm and oocyte are transcriptionally silent. The ensuing onset of embryonic transcription (embryonic genome activation [EGA]) is critical for development, yet its timing and profile remain elusive in any vertebrate species. We here dissect transcription during EGA by high-resolution single-cell RNA sequencing of precisely synchronized mouse one-cell embryos. This reveals a program of embryonic gene expression (immediate EGA [iEGA]) initiating within 4 h of fertilization. Expression during iEGA produces canonically spliced transcripts, occurs substantially from the maternal genome, and is mostly downregulated at the two-cell stage. Transcribed genes predict regulation by transcription factors (TFs) associated with cancer, including c-Myc. Blocking c-Myc or other predicted regulatory TF activities disrupts iEGA and induces acute developmental arrest. These findings illuminate intracellular mechanisms that regulate the onset of mammalian development and hold promise for the study of cancer.
