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Deciphering lineage specification during early embryogenesis in mouse gastruloids using multilayered proteomics.
Suzan Stelloo1, Maria Teresa Alejo-Vinogradova1, Charlotte A G H van Gelder2
1Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen, 6525 GA Nijmegen, the Netherlands.
Cell Stem Cell
|May 16, 2024
Summary
This study reveals dynamic protein expression during embryonic germ layer formation using gastruloids. It identifies key factors like ZEB2 crucial for somitogenesis in mammals.
Area of Science:
- Developmental Biology
- Proteomics
- Systems Biology
Background:
- Gastrulation establishes germ layers, crucial for embryonic development.
- Gene regulatory programs are known, but proteome-level data in early mammalian development is limited.
Purpose of the Study:
- To investigate global protein expression dynamics during gastruloid differentiation.
- To identify key regulators of germ layer development and somitogenesis.
Main Methods:
- Multilayered mass spectrometry-based proteomics of gastruloids.
- Single-cell proteomics validation.
- P300 proximity labeling for enhancer interactions.
- Degron-based perturbations with single-cell RNA sequencing (scRNA-seq).
Main Results:
- Identified proteins with temporal expression and unique profiles for each germ layer.
- Discovered gastruloid-specific transcription factors and chromatin remodelers.
- Demonstrated ZEB2's critical role in mouse and human somitogenesis.
Conclusions:
- Provides a comprehensive proteomic resource for understanding mammalian embryogenesis.
- Highlights the utility of gastruloids for studying early development.
- Identifies ZEB2 as a key regulator in somitogenesis.
