1. Deciphering lineage specification during early embryogenesis in mouse gastruloids using multilayered proteomics.
- Author
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Stelloo S, Alejo-Vinogradova MT, van Gelder CAGH, Zijlmans DW, van Oostrom MJ, Valverde JM, Lamers LA, Rus T, Sobrevals Alcaraz P, Schäfers T, Furlan C, Jansen PWTC, Baltissen MPA, Sonnen KF, Burgering B, Altelaar MAFM, Vos HR, and Vermeulen M
- Subjects
- Animals, Mice, Gene Expression Regulation, Developmental, Humans, Single-Cell Analysis, Cell Differentiation, Gastrula metabolism, Gastrulation, Proteomics, Embryonic Development genetics, Cell Lineage
- Abstract
Gastrulation is a critical stage in embryonic development during which the germ layers are established. Advances in sequencing technologies led to the identification of gene regulatory programs that control the emergence of the germ layers and their derivatives. However, proteome-based studies of early mammalian development are scarce. To overcome this, we utilized gastruloids and a multilayered mass spectrometry-based proteomics approach to investigate the global dynamics of (phospho) protein expression during gastruloid differentiation. Our findings revealed many proteins with temporal expression and unique expression profiles for each germ layer, which we also validated using single-cell proteomics technology. Additionally, we profiled enhancer interaction landscapes using P300 proximity labeling, which revealed numerous gastruloid-specific transcription factors and chromatin remodelers. Subsequent degron-based perturbations combined with single-cell RNA sequencing (scRNA-seq) identified a critical role for ZEB2 in mouse and human somitogenesis. Overall, this study provides a rich resource for developmental and synthetic biology communities endeavoring to understand mammalian embryogenesis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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