This shows that transient heterogeneity establishes a regulatory framework essential for proper intestinal regeneration and could be a general principle underlying a wide range of regenerative processes.

And validated in vivo!

We developed mathematical models showing how YAP1 and FOXA1 drive bistable states, allowing cells to "lock in" their fates. A feedback loop ensures long-term pattern stability and confers memory to the system.

And FOXA1 role is essential to exit a default state of differentiation.

YAP1 heterogeneity primes secretory progenitor cells, setting the stage for robust patterning. This involves chromatin remodelling, creating a favourable environment for FOXA1, a critical transcription factor.

When tissue density hits a critical level, YAP1 activity becomes heterogeneously inactivated. This cell-to-cell variability is essential for triggering the first cell fate decisions via chromatic remodelling and Delta-Notch signalling.

And the movie!

We also made a Yap activity fluorescent reporter organoid line to look into the dynamics at the tissue scales!

Using in vitro organoids and in vivo mouse models, we uncovered that mechanosensor YAP1 acts as a molecular "pre-patterner" cue during regeneration.

Amazing work @cschwayer.bsky.social @silviabarbiero.bsky.social @davidbrueckner.bsky.social @ehannezo.bsky.social

Tissue regeneration is driven by cells transitioning from homogenous regenerative cells to a patterned crypt. But actually cell-to-cell variability plays a super important role for the return to homeostasis!