Vinay Ayyappan

See this? This = implanting mouse embryo. Usually this happens inside its mother and is invisible to us, but we can actually watch implantation ex vivo with the hope of understanding why implantation goes awry in embryos of older women. A 🧵...

In this intriguing paper published from the lab of @amartinezarias.bsky.social , they looked at the effects of size on morphology, tissue composition, and gene expression of gastruloid development. They found that AP elongation dynamics is size-dependent! Check it out here:
doi.org/10.1016/j.cd...

Aria Huang's @azyhuang.bsky.social paper is out on beautiful embryonic kidney 3D cultures that branch properly and enable live defect analysis. She also finds intriguing effects of adhesion and stiffness on explant size, shape, and nephron formation - boundary conditions matter!

rdcu.be/eBSUK

@hugheslabpenn.bsky.social thank you so much!!! It’s been beyond a joy to work on it

Single-cell spatial mapping reveals reproducible cell type organization and spatially-dependent gene expression in gastruloids Gastruloids are three-dimensional stem-cell-based models that recapitulate key aspects of mammalian gastrulation, including formation of an anterior-posterior (AP) axis. However, we do not have detail...

[8/8] Huge thanks to all co-authors and the lab from whom I’ve learned so much, @arjunraj.bsky.social for so much mentorship and support. Particular shoutout to Cat, whose preprint also dropped. It’s amazing and everybody should check it out: www.biorxiv.org/content/10.1...

[7/8] We think morphogen signaling partly governs how clones partition tasks in gastruloid development. Adding Retinoic Acid to chimeric gastruloids caused clones to mix together, and inhibiting Nodal signaling disrupted propensity, even though clones stayed separated from one another.

[6/8] We integrated our lineage-tracing with spatial transcriptomics. Pure-clone gastruloids poorly organize marker gene expression. Combined-clone gastruloids have marker gene expression that is more comparably organized to bulk gastruloids.

[5/8] Instead of each clone trying to form all tissue types, biased clones focus on what they do best, and together they collectively organize more accurately than any individual clone could achieve alone.

[4/8] We think this is a form of “division of labor” among biased clones, which specialize in forming certain tissues. Kinda like Adam Smith’s example of workers in a pin factory. Every worker CAN do any task, but is better at some than others. Divvying-up the work boosts output.

[3/8] Mixing clones together also helps gastruloids elongate properly, and again, each clone takes its preferred spot along the anterior-posterior axis, effectively partitioning the job of making the gastruloid among themselves.

[2/8] Every clone has a preferred location in the chimeric gastruloid. Some have a propensity for the anterior, some for the posterior. Here, that propensity held in nearly every gastruloid over several rounds of aggregation.

[1/8] We used a fluorescence-based lineage tracing approach to track individual clones in a polyclonal aggregate. Pure clones are worse at forming gastruloids. But crazily enough, if you mix them with the original bulk population, they do great!

Gastruloid patterning reflects division of labor among biased stem cell clones Embryonic development typically requires precise coordination among cells to achieve reproducible outcomes, leading to the assumption that cellular heterogeneity must be minimized or buffered against....

[0/8] Stoked to share our work with @arjunraj.bsky.social on tissue organization in the gastruloid. We use lineage tracing and spatial transcriptomics to show that diversity among stem cell clones promotes, rather than hinders, gastruloid development: www.biorxiv.org/content/10.1...

Excellent work indeed, but I feel in this context @adrianobolondi.bsky.social fantastic work should also be mentioned www.cell.com/developmenta...

Two new preprints from the @arjunraj.bsky.social‬ on #gastruloids. Both excellent. Exploring the relationship between macroscopic reproducibility v microscopic heterogeneity. Stunning experiments and much to think about
biorxiv.org/content/earl...
biorxiv.org/content/earl...