TY - JOUR
T1 - Deciphering lineage specification during early embryogenesis in mouse gastruloids using multilayered proteomics
AU - Stelloo, Suzan
AU - Alejo-Vinogradova, Maria Teresa
AU - van Gelder, Charlotte A G H
AU - Zijlmans, Dick W
AU - van Oostrom, Marek J
AU - Valverde, Juan Manuel
AU - Lamers, Lieke A
AU - Rus, Teja
AU - Sobrevals Alcaraz, Paula
AU - Schäfers, Tilman
AU - Furlan, Cristina
AU - Jansen, Pascal W T C
AU - Baltissen, Marijke P A
AU - Sonnen, Katharina F
AU - Burgering, Boudewijn
AU - Altelaar, Maarten A F M
AU - Vos, Harmjan R
AU - Vermeulen, Michiel
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/7/5
Y1 - 2024/7/5
N2 - 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.
AB - 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.
KW - ZEB2
KW - dTAG system
KW - developmental biology
KW - enhancers
KW - gastruloids
KW - germ layers
KW - interaction proteomics
KW - proteomics
KW - somitoids
KW - transcription factors
UR - http://www.scopus.com/inward/record.url?scp=85194567564&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2024.04.017
DO - 10.1016/j.stem.2024.04.017
M3 - Article
C2 - 38754429
SN - 1934-5909
VL - 31
SP - 1072-1090.e8
JO - Cell stem cell
JF - Cell stem cell
IS - 7
ER -