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

doi:10.1016/j.celrep.2023.112023

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

Department of Life Sciences

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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 language	English
Article number	112023
Journal	Cell Reports
Volume	42
Issue number	2
Early online date	31 Jan 2023
DOIs	https://doi.org/10.1016/j.celrep.2023.112023
Publication status	Published - 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

General Biochemistry,Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.celrep.2023.112023Licence: CC BY

Cite this

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title = "A program of successive gene expression in mouse one-cell embryos",

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.",

keywords = "CP: Developmental biology, EGA, cancer, embryonic genome activation, fertilization, human genome editing, single-cell RNA-seq, transcription",

author = "Maki Asami and Lam, {Brian Y. H.} and Martin Hoffmann and Toru Suzuki and Xin Lu and Naoko Yoshida and Ma, {Marcella K} and Kara Rainbow and Miodrag Gu{\v z}vi{\'c} and Vermilyea, {Matthew D.} and Yeo, {Giles S. H.} and Klein, {Christoph A.} and Perry, {Anthony C. F.}",

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.",

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doi = "10.1016/j.celrep.2023.112023",

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T1 - A program of successive gene expression in mouse one-cell embryos

AU - Asami, Maki

AU - Lam, Brian Y. H.

AU - Hoffmann, Martin

AU - Suzuki, Toru

AU - Lu, Xin

AU - Yoshida, Naoko

AU - Ma, Marcella K

AU - Rainbow, Kara

AU - Gužvić, Miodrag

AU - Vermilyea, Matthew D.

AU - Yeo, Giles S. H.

AU - Klein, Christoph A.

AU - Perry, Anthony C. F.

N1 - 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.

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Y1 - 2023/2/28

N2 - 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.

AB - 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.

KW - CP: Developmental biology

KW - EGA

KW - cancer

KW - embryonic genome activation

KW - fertilization

KW - human genome editing

KW - single-cell RNA-seq

KW - transcription

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U2 - 10.1016/j.celrep.2023.112023

DO - 10.1016/j.celrep.2023.112023

M3 - Article

SN - 2211-1247

VL - 42

JO - Cell Reports

JF - Cell Reports

IS - 2

M1 - 112023

ER -

A program of successive gene expression in mouse one-cell embryos

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

New perspectives on imprinting disease

Switchable Gene Drives

Novel Homology-Directed Gene Targeting to Enhance Biomedical Modelling

Cite this

A program of successive gene expression in mouse one-cell embryos

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

New perspectives on imprinting disease

Switchable Gene Drives

Novel Homology-Directed Gene Targeting to Enhance Biomedical Modelling

Cite this