8/ scRNA sequencing, imaging and theory showed that large organoid monolayers exhibit a biosynthetic arrest at the center, followed by a loss of stemness and death (A pattern observed in vivo by
@batllelab.bsky.social
linkinghub.elsevier.com/retrieve/pii... )

7/ Surprisingly, hierarchy also emerges in vitro above a critical size defined by the intrinsic characteristic length of the stem cell compartment.
Below critical size ➡️ homogeneous proliferation
Above critical size ➡️ hierarchy

6/ But tumor patterning is more complex than just stem- and fetal-like states...

Above a critical tumor size, proliferation and death become spatially compartmentalized: cells divide at the edge and die at the core — a pattern typically attributed to hypoxia.

5/ Indeed!
Stress measurements (in vivo & in vitro) show a correlation between compression and Lgr5. With
Jochen's Guck Lab
.
To test causality, we physically confined organoids and tumors — and confinement alone was sufficient to boost stemness! With
Julie Guillermet Lab

4/ The interplay between proliferation and expansion generates cell density gradients from tumor edge to core. Interestingly, stem cells appear at high densities and fetal-like cells at low densities.

Could emergent mechanical gradients coordinate tumor cell state transitions?🤔

3/ Colorectal cancer organoid monolayers spontaneously recapitulate the tumor spatiotemporal patterning of stem (Lgr5) and fetal-like (Sca1) states, despite growing in homogeneous genetic and microenvironmental conditions.

Which signals pattern cell states in this context? 🤔

1/ 🎉Excited to share our new preprint @vignjeviclab.bsky.social @davidbrueckner.bsky.social :

"Self-organization of tumor heterogeneity and plasticity"
biorxiv.org/content/10.1...

Tumor heterogeneity and plasticity drive metastasis and relapse. How is tumor patterning coordinated?

A thread👇