Vinay Ayyappan
vayyappan.bsky.social
Vinay Ayyappan
@vayyappan.bsky.social
Penn MD/PhD student.
Runner when bones work
@hugheslabpenn.bsky.social thank you so much!!! It’s been beyond a joy to work on it
July 16, 2025 at 9:17 AM
[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...
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...
www.biorxiv.org
July 15, 2025 at 3:44 PM
[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.
July 15, 2025 at 3:44 PM
[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.
July 15, 2025 at 3:44 PM
[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.
July 15, 2025 at 3:44 PM
[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.
July 15, 2025 at 3:44 PM
[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.
July 15, 2025 at 3:44 PM
[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.
July 15, 2025 at 3:44 PM
[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!
July 15, 2025 at 3:44 PM