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Multiplexed Single Cell mRNA Sequencing Analysis of Mouse Embryonic Cells
Published on: January 7, 2020
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A program of successive gene expression in mouse one-cell embryos
Maki Asami1, Brian Y H Lam2, Martin Hoffmann3
1Laboratory of Mammalian Molecular Embryology, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.
Cell Reports
|February 2, 2023
Summary
Early embryonic gene activation (EGA) begins within 4 hours of fertilization in mice, involving maternal genome expression and regulated by factors like c-Myc, crucial for mammalian development.
Area of Science:
- Developmental Biology
- Genomics
- Molecular Biology
Background:
- Sperm and oocyte are transcriptionally silent at fertilization.
- Embryonic genome activation (EGA) is critical for development but poorly understood.
- The precise timing and profile of EGA in vertebrates remain elusive.
Purpose of the Study:
- To dissect the timing and profile of transcription during EGA.
- To identify the regulatory mechanisms governing the onset of embryonic transcription.
- To investigate the role of specific transcription factors in early development.
Main Methods:
- High-resolution single-cell RNA sequencing of synchronized mouse one-cell embryos.
- Analysis of gene expression patterns within 4 hours of fertilization.
- Functional experiments blocking transcription factor activity.
Main Results:
- Identified a program of immediate EGA (iEGA) starting within 4 hours of fertilization.
- iEGA involves canonically spliced transcripts, with significant maternal genome contribution.
- iEGA is downregulated by the two-cell stage and regulated by cancer-associated transcription factors like c-Myc.
- Blocking c-Myc or other TFs disrupts iEGA and causes developmental arrest.
Conclusions:
- Elucidated the early molecular mechanisms regulating the onset of mammalian development.
- Demonstrated the critical role of iEGA and specific transcription factors in early embryonic gene expression.
- Findings provide insights into developmental processes and potential links to cancer biology.
