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

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Abstract

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.

Original languageEnglish
Article number112023
JournalCell Reports
Volume42
Issue number2
Early online date31 Jan 2023
DOIs
Publication statusPublished - 28 Feb 2023

Bibliographical note

Funding Information:
We thank the University of Bath Animal Facility support staff and C. Tickle and M. Leeb for comments during manuscript preparation. We acknowledge support to A.C.F.P. from the UK Medical Research Council ( G1000839 , MR/N000080/1 , MR/N020294/1 , and MR/W024845/1 ) and Biotechnology and Biological Sciences Research Council ( BB/P009506/1 ) and to C.A.K. from the Josef Steiner Foundation and ERC grant 322602 . B.Y.H.L. is supported by BBSRC project grant BB/S017593/1 and B.Y.H.L. and G.S.H.Y. by the MRC Metabolic Diseases Unit (MC_UU_00014/1) . Next-generation sequencing was performed by the IMS Genomics and transcriptomics core facility, supported by the MRC ( MC_UU_00014/5 ), the Wellcome Trust ( 208363/Z/17/Z ), and the Cancer Research UK Cambridge Institute Genomics Core .

Data and code availability
The sequencing data generated in this study have been deposited in the NCBI GEO database under the accession number listed in the key resources table. Microarray data generated for this study have been deposited in the Gene Expression Omnibus (GEO) repository under accession numbers GEO: GSE64648, GEO: GSE64649, and GEO: GSE64650. Single-cell RNA-seq data generated for this study have been deposited under the accession numbers GEO: GSE157834 and GEO: GSE222130. This paper analyzes existing, publicly available data. The accession numbers for the datasets are listed in the key resources table.
This paper does not report original code.
Additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Keywords

  • CP: Developmental biology
  • EGA
  • cancer
  • embryonic genome activation
  • fertilization
  • human genome editing
  • single-cell RNA-seq
  • transcription

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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