Hans Clevers

by Hans Clevers

Hans Clevers

@hansclevers.bsky.social

bsky.app/profile/thec...

thecleverslab.bsky.social @thecleverslab.bsky.social · Sep 5

4/4 This work was a true team effort between @amolf-nl.bsky.social, IHB Basel, and the @Hubrechtinstitute.bsky.social — led by @danielkrueger.bsky.social and Kasper Spoelstra. Huge thanks to all collaborators for making it possible.

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by Hans Clevers

Hans Clevers

@hansclevers.bsky.social

11/11Gut homeostasis is not passive crowd control. It’s an active, force-regulated process. Cells constantly test each other’s strength; those that fail the tug-of-war extrude.A collaboration between the @hubrechtinstitute.bsky.social , @amolf-nl.bsky.social & @IHB lead by @danielkrueger.bsky.social

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by Hans Clevers

Hans Clevers

@hansclevers.bsky.social

10/11 Disease link: In EpCAM loss (tufting enteropathy), hyperactive myosin caused excessive extrusion, growth defects, and tissue disruption. Too much force destabilizes the barrier. Mixing mutant & WT cells made healthy cells extrude. Myosin inhibition rescued this effect.

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by Hans Clevers

Hans Clevers

@hansclevers.bsky.social

9/11 With point ablations at the base, we intentionally weakened individual cells. Within minutes, these cells extruded - loss of tension likely triggers extrusion.

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by Hans Clevers

Hans Clevers

@hansclevers.bsky.social

8/11 Local optogenetic activation of cells on villus substrates, creating boundaries between highly- and less-contractile cells caused preferential extrusion on the weaker side. In mosaic organoids, less contractile cells were consistently eliminated.

"Weaker" less contractile cells that can not sustain the tension level of their neighbours in the tissue preferentially extruded.

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by Hans Clevers

Hans Clevers

@hansclevers.bsky.social

7/11 Optogenetics let us induce contractility with blue light and spatial precision. Extrusion rates jumped up upon activation, showing that globally increased tension directly drives extrusion.

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by Hans Clevers

Hans Clevers

@hansclevers.bsky.social

6/11 A basal actomyosin network drives epithelial tension. On hydrogel villus substrates (generated @ IHB, Basel), resembling the in vivo topology, we saw pulsatile contractions—one cell contracts, neighbors expand. A tissue-wide tug-of-war.

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by Hans Clevers

Hans Clevers

@hansclevers.bsky.social

5/11 Using CRISPR-generated myosin reporters, we first observed myosin increasing in extruding cells, together with a synchronized response in their neighbors—explaining extrusion dynamics as a coordinated process.

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by Hans Clevers

Hans Clevers

@hansclevers.bsky.social

4/11 Are villus tips—where extrusion peaks—compressed by crowding? At the Hubrecht, laser ablation revealed they are under tension, not compression. That tension sets the stage for extrusion.

Laser ablation at the villus tip revealed that the tissue is under tension and cells are not under compression.

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by Hans Clevers

Hans Clevers

@hansclevers.bsky.social

3/11 Using long-term live imaging & tracking (with @amolf-nl.bsky.social), we followed hundreds of extrusion events. Most villus cells extruded alive, not apoptotic. Extrusion did not correlate with density.

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by Hans Clevers

Hans Clevers

@hansclevers.bsky.social

2/11 The intestinal lining renews every few days. Old cells are shed by extrusion—a process essential for barrier integrity and linked to diseases like IBD. But what actually triggers extrusion in mammals was unclear.

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by Hans Clevers

Hans Clevers

@hansclevers.bsky.social

1/11 In @science.org: A new perspective on how our intestines renew. Cells are not “pushed out” by crowding or die from apoptosis. Instead, cells play a mechanical tug-of-war, where weaker cells extrude, reframing gut renewal as force-regulated. www.science.org/doi/10.1126/...

Epithelial tension controls intestinal cell extrusion

Cell extrusion is essential for homeostatic self-renewal of the intestinal epithelium. Extrusion is thought to be triggered by crowding-induced compression of cells at the intestinal villus tip. In th...

www.science.org

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Reposted by: Hans Clevers

thecleverslab.bsky.social

@thecleverslab.bsky.social

4/4 This work was a true team effort between @amolf-nl.bsky.social, IHB Basel, and the @Hubrechtinstitute.bsky.social — led by @danielkrueger.bsky.social and Kasper Spoelstra. Huge thanks to all collaborators for making it possible.

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by Hans Clevers

Hans Clevers

@hansclevers.bsky.social

Brain diseases are tough to treat because of the blood-brain barrier. For decades, it stumped drug delivery. At Roche pRED, we challenged that! Our Brainshuttle™ technology safely transports drugs across, opening new doors for CNS therapies. Learn more: www.roche.com/stories/clev...

Roche | Clever delivery

Brainshuttle™ technology by Roche enables effective medicine delivery across the blood-brain barrier, revolutionising CNS disease treatment and patient care.

www.roche.com

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by Hans Clevers

Reposted by: Hans Clevers

by Hans Clevers

Reposted by: Hans Clevers

by Hans Clevers

Hans Clevers

@hansclevers.bsky.social

Exciting #organoids meeting in Glasgow, just after the summer!

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by Hans Clevers

Hans Clevers

@hansclevers.bsky.social

🔬 Developing next-generation Antibiotics: @Roche we are pioneering the discovery and development of novel antibiotics that can fight resistant bacteria, aiming for future generations to have effective treatments. Visit our #AMR hub:https://www.roche.com/stories/antibiotics

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by Hans Clevers

Reposted by: Hans Clevers

by Hans Clevers

Hans Clevers

@hansclevers.bsky.social

@NatureMedicine
invited me to reflect on leading research in academia vs. industry. In the end, all -academia, biotech & pharma- is needed to translate scientific breakthroughs into scalable treatments. rdcu.be/elPt8
@_hubrecht
@Roche

Parallel worlds in pharma and academia

Nature Medicine - Pharma and academia require different ways of working and speaking, but teamwork always wins.

rdcu.be

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References

Fields & subjects