Hubrecht Institute, Utrecht, The Netherlands
Based in Italy
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Using snake airway organoids, we modelled reptile virus infection in vitro. With a new Python Regius reference genome, we show that our organoids contain multiple cell types, could mount an immune response and respond to antivirals.
Paper: nature.com/articles/s41467-0…
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4/4 This work was a true team effort between @_amolf, @ihb_research, and the @_Hubrecht — led by @DanielKruegerDK and Kasper Spoelstra. Huge thanks to all collaborators for making it possible.
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3/4 This reveals a safeguard mechanism: epithelial cells constantly test each other’s mechanical strength. Too little (or too much) force destabilizes the barrier, linking extrusion to diseases like tufting enteropathy. Gut renewal is an active, force-regulated process.
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2/4 New in Science: Using live imaging, CRISPR myosin reporters, organoid villus substrates & optogenetics, we found that myosin-driven tissue tension—not compression—controls extrusion. Cells with reduced contractility are preferentially removed.
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Our PhD student Sam presented our work on thymus organoids at this year’s Global Thymus Network meeting, ThymUS 2025.
#ThymUS2025 #Organoids #Thymus
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📢New human fetal pancreatic organoid model generates all three key cell types of the pancreas. New paper in @CellCellPress by @AmandaARolf , @HansClevers and collaborators. See the article here: sciencedirect.com/science/ar…
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Watch back the 2024 EMBL Kafatos Lecture where @HansClevers presented about the application of organoids in disease modeling at the @_knaw Amsterdam. #embl #knaw #organoids piped.video/watch?v=eePX-My4…
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One bacterial protein as a complement to #Matrigel/#BME: The #integrin -binding domain of the Yersinia bacterial protein Invasin, coated as a single protein, maintains a defined long-term culture of various epithelial cells as “2D #organoid sheets”.
biorxiv.org/content/10.1101/…
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The Clevers lab is represented at the #ERSCongress in Vienna, with @nella_dost presenting her primary human alveolar lung organoid model @EuroRespSoc #organoid
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The clevers lab is at the EMBL organoid symposium. Come see our posters today and tomorrow.
Todays posters are: 75, 147, 169
Tomorrows poster are: 52, 64, 162, 252, 254
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Carla presenting her work on human kidney tubuloids at the ASN Kidney Week in Orlando, Florida!
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The role of BMP in the zonation was confirmed in human organoids and mice with BMP receptor knockouts, both of which lost the capacity to produce cells with the villus tip functional phenotype.
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Similarly, goblet cells change the expression of antimicrobial peptides between BMP-on and -off states.
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In enterocytes, we find that BMP induces a shift towards a villus tip cell state characterized by lipid uptake and loss of antimicrobial peptides.
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We combined human intestinal organoids, CRISPR engineering, mouse models and single cell RNA sequencing to test multiple intestinal morphogens and show that BMP controls this zonation.
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Intestinal cells change their function over their lifetime, regulated by BMP signaling. New paper just out in @CellReports by @BeumerJoep, @JensPuschhof, Fjodor Yousef Yengej, @HansClevers and collaborators! Interested in the details? A thread (1/x):
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We're looking forward to @HansClevers presentation at the "Lab of the Future Live" on October 26th & 27th. You can join for this free event at: lab-of-the-future.com/europe… #labofthefuture #innovation #lifesciences #digitalization
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We can use this organoid biobank to rapidly screen host factor dependency in any emerging coronavirus or SARS-CoV-2 variants in the future.
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Other host factors that were previously linked to coronavirus replication were not affecting SARS-CoV-2 replication. This points to high level of redundancy in many of these host factors.
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Chloroquine as well as proteases involved in putative the endocytosis entry pathway of SARS-CoV-2 did not appear to affect infectivity. This reconfirms the importance of plasma membrane entry in these epithelial cells.
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One set of genes we focused on were proteases that cleave the spike protein of Coronaviruses. These experiments indicate SARS-CoV-2 predominantly enters epithelial cells through the plasma membrane in a TMPRSS2-dependent manner.
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As a proof of principle we infected organoid lines mutant for ACE2 (entry receptor of SARS-CoV/SARS-CoV-2) and DPP4 (entry receptor for MERS-CoV). Loss of these receptors fully prohibited infection with the corresponding virusses. This establishes the validity of the approach.
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Next, after genotyping thousands of organoid clones we generated a biobank of clonal CRISPR-engineered organoid lines containing homozygous loss-of function mutations in these host factors.
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First we report expression profiles of coronavirus host factors (derived from previous studies that mostly involve 2D cell lines) in different adult stem cell-derived organoid models by single-cell RNA sequencing and compared these to tissue.
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Two members from the Clevers lab will be presenting their work on exciting new #organoid models at #ISSCR2021(details below). Congratulations to @Marie_Bannier and @TalyaDayton for also winning the Zhongmei Chen Yong Award for Scientific Excellence and an Abstract Merit Award!
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At this moment, @HansClevers is having his induction ceremony as Honorary Fellow of The Royal Society of Edinburgh. The RSE was established in 1783 for the advancement of 'learning and useful knowledge'.
ALT RSE building , credit: Ryan Johnston
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The @NatureProtocols on #kidney tubuloids and tubuloid cells on a chip came online minutes ago: nature.com/articles/s41596-0…
Great work by Clevers lab PhD Fjodor Yousef Yengej, Linda Gijzen and many other colleagues at @TheCleversLab, @MIMETAS_3D and beyond.
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Congratulations to @HansClevers for receiving an honorary doctorate from @KU_Leuven today!
Read the full interview below:
stories.kuleuven.cloud/en/st…
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One of the great 2020 additions to the lab is Elena, who joined as a Postdoc. She is a Chemical Biologist by training and combines her background with organoid technology to study drug and nutrient uptake in the intestine.#ChemicalBiology #organoids #Malabsorption #DrugUptake
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Mystery organoid 1 was hiding the real Clevers organoid tree! Long known for its sophisticated office culture, the "other side" office 8 has accumulated a Christmas tree fully decorated with organoid pictures and model organisms over the years.
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Our lab Christmas card is already in great shape thanks to MSc student @NinoukAkkerman. Curious what is hiding behind the 7 mysterious organoids? Stay tuned!
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Wim de Lau makes Christmas great again in the Clevers lab. #shakingtree
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There it is! Congratulations to @kadi_est for successfully defending an outstanding PhD thesis this week.
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#kadi_est will be defending her thesis tomorrow at 9:15 CET. The entire lab wishes her the best of luck!! Anyone interested can follow the entire ceremony using the following link: live.starleaf.com/ODQxMDg6MD…
Edu Kadi! 💪💪
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A virtual event organized by #thermofisher on 3D models for academia and industry Nov 10-12, #HansClevers and Rob Vries will be giving keynotes. You can still register at thermofisher.com/3daysof3d
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We are very proud to announce that #HansClevers will be taking part at the 2020 World Laureates Forum in Shanghai, starting tomorrow. This gathering of scientists across the globe is the highest-profile scientific conference in Asia, aiming to advocate for science worldwide.
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A creative thank you and goodbye to the lab by Kadi Lõhmussaar!
She will be defending her thesis next month, on organoids from the female reproductive system. We wish her all the best for the preparations and her future work in the @JensenLab_UCPH.
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Yesterday (Californian night), @PostYorick showed an excellent performance during the defence of his thesis, organoids across the animal kingdom. @freekvonk congratulated Yorick during the subsequent online celebrations in the following way (from a studio).
Yorick Post defended his thesis this morning (his midnight) from San Francisco. #snakevenom #cardiacstemcells #teargland. Entirely virtual, which was at moments a bit awkward, but it went very well. Cum laude!
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Being physically separated from our #organoids, the group embarked on some #stemcell-themed haiku writing. Starting with a very nice one by MSc student Ninouk Akkerman:
𝗧𝗵𝗲 𝗰𝗿𝘆𝗽𝘁'𝘀 𝗰𝗮𝗹𝗹
Voices of the Wnt
Singing soft from Paneth's lair
Rise up young forebears!
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Adding ovarian cancer to the organoid toolbox.
Congratulations to Kadi Lõhmussaar, Oded Kopper and many others from the Clevers lab on their paper just out in @NatureComms! go.nature.com/3gsrI4O
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A deep look into the gut's hormones. Paper just out in @CellCellPress, led by PhD students @BeumerJoep and @JensPuschhof from @HansClevers group.
Amazing group effort, with 16 co-authors from the Clevers lab (marked in yellow, must be a record) and a great group of collaborators!
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While we can't go to the lab these days, nothing can stop us from a Clevers group board game night via Skype😃
Great initiative by PhD student Jelte van der Vaart!
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And here's the team leading the recent #CRISPR-HOT cover story in @NatureCellBio: Postdocs Delilah Hendriks (left) and Benedetta Artegiani (right).
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Big congratulations to Benedetta Artegiani and Delilah Hendriks: Their hot new #CRISPR-HOT method for fast and easy generation of knock-in reporters in #organoids just made the cover in @NatureCellBio!
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New study in Nature by Clevers PhD students Cayetano Pleguezuelos-Manzano, @JensPuschhof and Axel Rosendahl Huber (Ruben van Boxtel lab):
Bacteria cause mutations in colorectal cancer genomes.
Read more at: nature.com/articles/s41586-0…
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It was a great night at @dwdd yesterday for @HansClevers and @freekvonk, presenting our snake venom gland organoid study (just out in @CellCellPress)!
Only @PostYorick missing for a perfect evening with the snake team. @BeumerJoep @JensPuschhof
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A new year and 4 great additions to our group! We welcome (from back to front): David Cleal (Marsala, MSc student), Leo Carrillo (Paris, MSc student), Aurelia Saftien (Konstanz, post-MSc intern) and Charel Boot (The Hague, analyst).
@_Hubrecht
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Behind the embryo award... Did you know our very own Jeroen Korving (Histology legend at @_Hubrecht and @TheCleversLab) has been designing and creating the trophies for 8 years?
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