Deciphering lineage specification during early embryogenesis in mouse gastruloids using multilayered proteomics

Suzan Stelloo, Maria Teresa Alejo-Vinogradova, Charlotte A G H van Gelder, Dick W Zijlmans, Marek J van Oostrom, Juan Manuel Valverde, Lieke A Lamers, Teja Rus, Paula Sobrevals Alcaraz, Tilman Schäfers, Cristina Furlan, Pascal W T C Jansen, Marijke P A Baltissen, Katharina F Sonnen, Boudewijn Burgering, Maarten A F M Altelaar, Harmjan R Vos, Michiel Vermeulen

Research output: Contribution to journal/periodicalArticleScientificpeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)1072-1090.e8
JournalCell Stem Cell
Volume31
Issue number7
DOIs
Publication statusPublished - 05 Jul 2024

Keywords

  • Animals
  • Proteomics
  • Mice
  • Embryonic Development/genetics
  • Cell Lineage
  • Gene Expression Regulation, Developmental
  • Humans
  • Single-Cell Analysis
  • Cell Differentiation
  • Gastrula/metabolism
  • Gastrulation

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