荷兰奈梅亨大学Oncode研究所Michiel Vermeulen团队报道，利用多层蛋白质组学技术破译小鼠类胃原肠早期胚胎发生过程中的谱系规范。相关论文发表在2024年5月15日出版的《细胞—干细胞》杂志上。

据了解，原肠胚形成是胚胎发育的关键阶段，胚层在此阶段形成。测序技术的进步导致了控制胚层及其衍生物出现的基因调控程序的鉴定。然而，基于蛋白质组的早期哺乳动物发育研究很少。

研究小组利用类胃原体和基于多层质谱的蛋白质组学方法，来研究类胃原体分化过程中(磷酸化)蛋白表达的全局动态。他们的发现揭示了许多具有时间表达的蛋白质和每个胚层的独特表达谱，研究人员也证实了单细胞蛋白质组学技术。

此外，课题组还利用P300邻近标记分析增强子相互作用图谱，揭示了许多类胃肠特异性转录因子和染色质重塑因子。随后基于退化的扰动结合单细胞RNA测序(scRNA-seq)，鉴定了ZEB2在小鼠和人类体细胞发生中的关键作用。总之，这项研究为理解哺乳动物胚胎发生发育和合成生物学提供了丰富的依据。

附：英文原文

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

Author: 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 Schfers, 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

Issue&Volume: 2024-05-15

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.

DOI: 10.1016/j.stem.2024.04.017

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(24)00144-9