iiinova — where your digital self keeps evolving

Reposted by Snippert lab

Hans Clevers @hansclevers.bsky.social · 10/05/2026

Short write-up of our journey. Searching for T cell transcription factors, Marc v/d Wetering stumbled across Wnt signaling. Vladja Korinek linked Wnt to colon cancer and crypt biology. Nick Barker discovered the gut stem cell. Toshi Sato invented organoids authors.elsevier.com/a/1n3No6tu0C...

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Reposted by Snippert lab

Joris Hageman @jorihag.bsky.social · 15/04/2026

Very proud to share our new paper on early cancer progression, published in Nature! Beyond the science itself, this project really shows what strong interdisciplinary collaboration can achieve. I feel grateful to have been part of this amazing team. Check out our discoveries below!

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Snippert lab @hugosnippert.bsky.social · 15/04/2026

Immense gratitude to the whole team and superior collaborators Leon Moons and Miangela Laclé. Big thanks to our funders @erc.europa.eu KWF ZonMw @oncodeinstitute.bsky.social @umcutrecht.bsky.social @themaximacenter.bsky.social

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Snippert lab @hugosnippert.bsky.social · 15/04/2026

And no, presence of oncofetal plasticity does not equate to metastatic disease 🔥 💣 🤯

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Snippert lab @hugosnippert.bsky.social · 15/04/2026

Fibroblast-organoid co-cultures 🧫 confirm that these trophocyte-like CAFs induce plastic transitioning to oncofetal states. Their interaction follows from invasive growth into the submucosa and dictates the timing and location at which oncofetal plasticity first occurs during CRC progression.

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Snippert lab @hugosnippert.bsky.social · 15/04/2026

Single-cell spatial atlases 🌍 of tumors pre-and post malignant transformation revealed stereotypic patterning of fibroblast subtypes resembling normal tissue architecture. Of interest: the first cancer-associated fibroblasts resembled submucosal trophocytes and colocalize with oncofetal cells

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Snippert lab @hugosnippert.bsky.social · 15/04/2026

To understand how invasive phenotypes first emerge, we generated multiregional organoid models that reflect successive tumor progression stages within individual early-stage CRCs. Whole-genome sequencing 🧬 and growth factor-dependency assays 💊 exclude tumor cell-intrinsic acquired traits.

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Snippert lab @hugosnippert.bsky.social · 15/04/2026

With @julian-buissant.bsky.social @jorihag.bsky.social Sascha Brunner and Suzanne van der Horst, we pivoted our focus to the earliest stages of cancer 🔬 Malignant transformation is a milestone in tumor evolution but still a "black box" My lab's ambition became prevention of metastatic disease 🙅

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Snippert lab @hugosnippert.bsky.social · 15/04/2026

Huge news! Our research is out in Nature✨ www.nature.com/articles/s41... We’ve uncovered that oncofetal plasticity in colorectal cancer arises far earlier than anyone expected. Providing a new lens on how cancers transition to metastatic disease. Big thanks to my team and collaborators!

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Reposted by Snippert lab

Joris Hageman @jorihag.bsky.social · 29/07/2025

I’m happy to share our new preprint on stem cell regeneration in the human colon! Using new CRISPR knockins in organoids, we show that after stem cell loss, non-stem cells rapidly regenerate them. This process is normally inhibited by the stem cells themselves. Manuscript link: tinyurl.com/3ky4ccxf

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Snippert lab @hugosnippert.bsky.social · 23/07/2025

6/ Many thanks to all co-authors, dear collaborators and funders. Especially the Dutch Research Council (NWO) for our ‘organoids in time’ consortium spearheaded by Jeroen van Zon

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Snippert lab @hugosnippert.bsky.social · 23/07/2025

5/ Our tuft subtype-specific reporters and optimized differentiation strategy in organoids provide an experimental platform to study immune-related tuft cell subtypes and their unique cell biological properties, like signal perception, processing and transmission to trigger immune defense.

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Snippert lab @hugosnippert.bsky.social · 23/07/2025

4/ Adaptation of the crypt-like organoid medium to better mimic the villus environment, where tuft-2 cells reside in vivo, facilitates transitioning of post-mitotic immature tuft-1 states to the mature immune-related tuft-2 states that is ready for in-depth cell biological studies.

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Snippert lab @hugosnippert.bsky.social · 23/07/2025

3/ Organoids with subtype-specific reporter knock-ins show that known tuft types in fact reflect successive maturation stages within the tuft lineage. Be aware 😱, commonly applied organoid treatment with IL-4 and 13 does lead to increased tuft numbers, but solely generates early tuft-1 states 🙅❌

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Snippert lab @hugosnippert.bsky.social · 23/07/2025

2/ We analyzed single-cell intestinal tuft cell transcriptomes from mouse and human to reveal conserved proliferative tuft cell precursors (tuft-p), as well as abundant intermediaries of the previously described post-mitotic tuft-1 and tuft-2 cell states.

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Snippert lab @hugosnippert.bsky.social · 23/07/2025

🔊 Paper alert 1/ Tuft cells are perhaps the coolest cells in our gut orchestrating host defense, but how do they manage? @julian-buissant.bsky.social provides new insights into tuft cell differentiation, and the development of accurate in vitro models for experimental cell biology 🧫🔬🧬 rdcu.be/exou9

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Snippert lab @hugosnippert.bsky.social · 23/07/2025

Thanks for the compliments Adam

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Snippert lab @hugosnippert.bsky.social · 16/07/2025

Big thanks to all our co-authors and in particular @jorihag.bsky.social for conceiving and spearheading this cool project 👏👏 🙌 💪

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Snippert lab @hugosnippert.bsky.social · 16/07/2025

8/ Thus, stem cell-derived retinoic acid actively suppresses plasticity in colonocytes, ensuring homeostasis and explaining how surviving cells sense stem cell loss. Please see preprint for detailed info. Concerning our favoured knock-in strategy, please see Bollen, Hageman et al., PLOS Biol 2022

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Snippert lab @hugosnippert.bsky.social · 16/07/2025

7/ Under homeostatic conditions, RXR is activated in colonocytes by RA produced by ALDH in stem cell compartments. But when the RA signal is lost (via stem cell loss or RXR inhibition), cells switch to an ANXA1-high regenerative state (visualized by independent ANXA1-RFP knock-in)

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Snippert lab @hugosnippert.bsky.social · 16/07/2025

6/ scRNA-seq and sc-multiome at high temporal resolution showed that predominantly surviving colonocytes first adopt a regenerative state marked by high ANXA1, before giving rise to new stem cells.

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Snippert lab @hugosnippert.bsky.social · 16/07/2025

5/ Stem cell depletion triggered an unbiased and fast response with surviving cells quickly regenerating the LGR5+ stem cell pool. (normal organoids carrying 2 knock-ins: LGR5-GFP-DTR x KRT20-RFP-iCasp9)

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Snippert lab @hugosnippert.bsky.social · 16/07/2025

4/ Next, knock-in of the Diphtheria Toxin Receptor into the LGR5 locus enabled selective stem cell ablation under normal conditions. Killing was robust, consistent and independent of low expression levels common to typical cell type markers (unlike inducible iCasp9)

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Snippert lab @hugosnippert.bsky.social · 16/07/2025

3/ First, we harnessed the power of genetic mouse models with selective cell type ablation. Except 😥, the widely used Diphtheria Toxin Receptor for cell killing is a common human receptor. 💡 We de-sensitised human organoids for D with a murinizing 🐭 point mutation in the endogenous entry factor.

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Snippert lab @hugosnippert.bsky.social · 16/07/2025

2/ We found that human colon stem cells produce retinoic acid (RA), which acts as a “keep calm and carry on” signal to neighbouring cells, actively blocking their entry into a regenerative state. It explains how surviving cells sense stem cell loss 🔥

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Snippert lab @hugosnippert.bsky.social · 16/07/2025

📢 New preprint 🔥 1/ Stem cell regeneration is often viewed as an actively induced process, triggered by damage. But what if plasticity is actively suppressed by the stem cells themselves? We explored plasticity with 'new' cell type ablation tech in normal human colon organoids tinyurl.com/3ky4ccxf

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Reposted by Snippert lab

Trevor Graham @trevorgraham.bsky.social · 07/03/2025

Our #Cancer #Evolution summer school runs again 30 June-3 July at the beautiful Genome Campus in Hinxton, UK sponsored by @wellcometrust.bsky.social Ideal for starters in the field; this year's focus is on using genomic data for cancer evo research. Brilliant & inspiring faculty! bit.ly/40nLdDD

bit.ly

Evolutionary Biology and Ecology of Cancer — 20250630

Evolutionary Biology and Ecology of Cancer

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Snippert lab @hugosnippert.bsky.social · 14/02/2025

📢 Organoid enthusiast: We are preparing for the 3rd edition of OrganoidNL - April 11th! 🔥 Check amazing line up of speakers 🔥 Calvin Kuo @priscaliberali.bsky.social Nicolas Rivron, Ina Sonnen @kaikretzschmar.bsky.social Mina Gouti, and others. Be fast to register in time amolf.nl/organoidnl-s...

amolf.nl

OrganoidNL Symposium - AMOLF

OrganoidNL Symposium 2025 Friday, April 11

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Reposted by Snippert lab

Philip Dunne @profpipdunne.bsky.social · 06/12/2024

Massive congrats to Shania, Svetlana & Noha (not on Bsky) identifying the mechanistic and phenotype cascades underpinning the anti-metastatic response triggered by viral mimicry TLDR; aggressive CMS4 tumours can be reprogrammed towards less aggressive CMS1 biorxiv.org/content/10.1... thread 👇

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Julian Buissant des Amorie @julian-buissant.bsky.social · 03/12/2024

Very happy that our tuft cell story is now on BioRxiv! If you want to know how to induce mature tuft cell phenotypes in organoids check out the preprint

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Reposted by Snippert lab

The Batlle Lab @batllelab.bsky.social · 02/12/2024

📢📢📢

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Snippert lab @hugosnippert.bsky.social · 01/12/2024

New work on #tuft cells, rare guardians of our #gut against invaders. How they work is not known. We show that intestinal tuft types 1&2 are sequentially expressed phenotypes during differentiation. And…we can now generate mature immune-related tuft-2’s in #organoids for more 🔬🧫🧬🔥 shorturl.at/EImjA

shorturl.at

Mature tuft cell phenotypes are sequentially expressed along the intestinal crypt-villus axis following cytokine-induced tuft cell hyperplasia

Intestinal tuft cells are epithelial sentinels that trigger host defense upon detection of parasite-derived compounds. While representing interesting targets for immunomodulatory therapies in inflamma...

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Snippert lab @hugosnippert.bsky.social · 01/12/2024

We thank all our co-authors to join us on our adventure and for their help! 👏👏 Big applause to our great first author @julian-buissant.bsky.social

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Snippert lab @hugosnippert.bsky.social · 01/12/2024

shorturl.at

Mature tuft cell phenotypes are sequentially expressed along the intestinal crypt-villus axis following cytokine-induced tuft cell hyperplasia

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Snippert lab @hugosnippert.bsky.social · 24/11/2024

Hey all, we are pretty new here Our team likes to be creative with #organoids to solve science questions that excite us. We mostly focus on early-stage colorectal #cancer using #patient #samples. We'll post new work soon 🔥. First an adventurous detour 😊 on #tuft cell differentiation, stay tuned…

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