Hans Clevers

@hansclevers.bsky.social

1.2K followers 22 following 30 posts

-Scientist interested in Wnt signaling, stem cells and organoids
-Director of pRED/Roche's Institute of Human Biology Basel CH.
-Professor and group leader in Utrecht at the Hubrecht Institute and the Princess Maxima Center .. more

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Johannes (Hans) Carolus Clevers is a Dutch molecular geneticist, cell biologist and stem cell researcher. He became the Head of Pharma, Research and Early Development, and a member of the Corporate Executive Committee, of the Swiss healthcare company Roche in 2022. Previously, he headed a research group at the Hubrecht Institute for Developmental Biology and Stem Cell Research and at the Princess Máxima Center; he remained as an advisor and guest scientist or visiting researcher to both groups. He is also a Professor in Molecular Genetics at Utrecht University. .. more

Biology 78%

Medicine 16%

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Reposted by Hans Clevers

Hans Clevers @hansclevers.bsky.social · Sep 6

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.

Hans Clevers @hansclevers.bsky.social · Sep 6

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

Hans Clevers @hansclevers.bsky.social · Sep 6

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.

Hans Clevers @hansclevers.bsky.social · Sep 6

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

Hans Clevers @hansclevers.bsky.social · Sep 6

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.

Hans Clevers @hansclevers.bsky.social · Sep 6

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.

Hans Clevers @hansclevers.bsky.social · Sep 6

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.

Hans Clevers @hansclevers.bsky.social · Sep 6

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.

Hans Clevers @hansclevers.bsky.social · Sep 6

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.

Hans Clevers @hansclevers.bsky.social · Sep 6

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.

Hans Clevers @hansclevers.bsky.social · Sep 6

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.

Hans Clevers @hansclevers.bsky.social · Sep 6

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

Reposted by Hans Clevers

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

Hans Clevers @hansclevers.bsky.social · Jul 31

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

Reposted by Hans Clevers

Hans Clevers @hansclevers.bsky.social · Jun 7

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

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