Very happy to share our latest w/ @dschweppe1 and @Nobu_Hamazaki labs, where we map the temporal dynamics and proteomic landscape of mammalian gastruloids. Sneek Peak 🧵below #stembryo #gastruloid #proteomics.

RT @BrotmanBaty: 'By building something new, we can have a deeper understanding of how that new creation functions.' Learn how Nobuhiko Ham….

Many thanks @BrotmanBaty for the chat. It's been great to be part of @uwgenome's vibrant research community and work with brilliant and supportive colleagues in @JShendure's and @lea_starita's labs!.

RT @dschweppe1: Great seeing this big collaborative effort come together with @lea_starita, @Nobu_Hamazaki, @JShendure, and led by @riddhim….

RT @AMartinezArias: Deluge of useful information @ proteomics, protein/mRNA correlations, comparative molecular landscapes and more. #gastr….

Last but by no means least, this work was catalyzed by both awesome colleagues Valerie Lynch, @Rose_B_Fields, Silvia Casadei, Sabrina Best, Jeremy Stone, Matthew Snyder, @CD_McGann as well as valuable resources from @uwgenome, @CEGS_CMAP, @BrotmanBaty.

As always, huge thanks to my mentors @JShendure and @lea_starita for their constant mentorship and for creating fantastic environments that bring exciting science to life!.

This has been a labour of love stemming from many insightful and stimulating conversations w/ @Nobu_Hamazaki and @dschweppe1 and wouldn’t be possible without unconditional support from them and their amazing labs!.

Looking forward, while it is still early days, we are living in exciting times of stembryo models and we hope that our resource (explorable at will contribute towards engineering the next generation of these models in the years ahead.

More broadly, it contributes to the growing body of work phenotyping the temporal proteomic changes in models of early embryonic development. See amazing resource by @Suz_Stelloo and the @LabVermeulen lab.

Finally, we map the temporal profiles of disease genes and often observe that these tend to be coregulated over gastruloid development thereby offering starting points to characterize their functional roles and identify coregulated partners in these developmental contexts.

We expand our multi-omics approach to uncover the temporal dynamics of phosphorylation states over the course of gastruloid development and suggest developmentally regulated kinase substrate pairs in the context of gastruloid development.

By integrating proteomic data with experimentally matched RNAseq datasets, we elucidate global and temporal discordance between RNA and protein abundance, revealing that peri-gastrulation stages tend to exhibit significant discordance, often linked to the mitochondrial proteome.

We build networks of coregulation across protein pairs thereby mapping both the extent of correlation within protein complexes and identify key cooperative proteins associating with them during mammalian gastruloid development.

We observe thousands of differentially expressed proteins between stages of gastruloid development and often observe that these tend to be coordinated temporal shifts in cellular modules across stages of gastruloid development.

To fill this gap, we use quantitative proteomics to map the temporal changes in the proteome across 4 key stages of gastruloid development spanning both pre- and post-implantation states in both mouse and human gastruloids.

However, the scarcity of assays at the protein level particularly mapping their dynamics and regulation has left a substantial gap in understanding the molecular and cellular rules driving these developmental processes.

Gastruloids have been extensively profiled with single-cell transcriptomics (scRNA-seq) and high-resolution imaging that have significantly advanced our understanding of these models.

@Nobu_Hamazaki and @VinetteY recently demonstrated that a discontinuous regimen of retinoic acid successfully induces human gastruloids with embryo-like structures, including neural tube and segmented somites.

In recent years, there has been a steady expansion in stem cell models of embryogenesis. “Gastruloids” are one such model that recapitulate features of gastrulation (i.e. proliferation, symmetry breaking, and germ layer specification) under defined culture conditions.

Obvious ethical and technical challenges have limited our ability to understand this stage of embryogenesis comprehensively. So, a longstanding goal towards understanding gastrulation and early embryogenesis has been modeling post-implantation development using stem cells.