Proteomics

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Deciphering lineage specification during early embryogenesis using multi-layered proteomics


ABSTRACT: Gastrulation is a critical stage of embryonic development during which the three germ layers are established. Deciphering the molecular mechanisms underlying this proces from a protein perspective remains a significant challenge. To address this, we employed a multilayered mass spectrometry-based proteomics approach to investigate the global dynamics of (phospho)protein expression during differentiation of ESCs towards gastruloids – an in vitro model of gastrulation-stage embryogenesis. Our findings revealed that many proteins exhibited temporal expression with unique expression profiles corresponding to the three germ layers. Additionally, we profiled enhancer interaction landscapes in ESCs and gastruloids using p300 proximity labeling, which revealed numerous gastruloid-specific transcription factors and chromatin remodelers. Subsequent degron based perturbations combined with scRNA-seq revealed a critical role for Zeb2 in regulating mouse and human somitogenesis. Overall, this study provides a rich resource for developmental and synthetic biology communities endeavoring to understand mammalian embryogenesis.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Embryonic Stem Cell

SUBMITTER: S Stelloo  

LAB HEAD: Michiel Vermeulen

PROVIDER: PXD041309 | Pride | 2024-05-21

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
20210325_Exploris1_SA_Suz_BFP1.raw Raw
20210325_Exploris1_SA_Suz_BFP2.raw Raw
20210325_Exploris1_SA_Suz_BFP3.raw Raw
20210325_Exploris1_SA_Suz_GFP1.raw Raw
20210325_Exploris1_SA_Suz_GFP2.raw Raw
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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 e  ...[more]

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