Sendoel Lab

Our first PhD generation is flying out of the nest. Thank you Merve and Clara for shaping our lab from day one on.

Wishing you all the best in your next chapters, we’re excited to see what comes next for you!

🔬✨ Join us this Saturday (September 6) | 16:00-23:00 at Nacht der Forschung 2025 at the University of Bern ✨ Come and check out our booth "RNA – Master of Versatility" 👩‍🔬

Meet our researchers & enjoy pipetted cocktails at the reproduzierBAR!
www.nachtderforschung.unibe.ch
#ndfunibern @unibe.ch

If you are interested in #DevBio, #organoids, #gastruloids or #CRISPR, check out the tweetorial to our new preprint on uncovering novel regulators of body plan formation in gastruloids using single cell CRISPR screens!

A big thank you to all co-authors that made this paper possible!

The authors report that all seven tested deep learning models failed to outperform simple baselines in predicting transcriptome changes after single or double perturbations.

I will duck for cover.

Genome-wide chromatin recording resolves dynamic cell state changes https://www.biorxiv.org/content/10.1101/2025.08.05.668773v1

Many thanks to all members of our lab and to our collaborators in the Lutolf and Zavolan labs!

In sum, our findings highlight polyadenylation-mediated control of transcript stability as a critical mechanism in shaping the mammalian body plan and position gastruloid-based single-cell CRISPR screening as a powerful platform for systematic discovery of developmental regulators.

Cells adopting notochord identity in Cnot8 KO gastruloids closely matched embryonic notochord cell profiles. This was accompanied by increased Nodal signaling and a profound loss of Hox gene expression, with a shift toward dorso-ventral and anterior primitive streak fates.

Single-cell RNA sequencing of Cnot8-deficient gastruloids demonstrated severely altered mesodermal patterning, with paraxial mesoderm largely absent and a bias toward axial mesoderm and notochord differentiation.

Intriguingly, Cnot8 KO organoids exhibited indeed transcript stabilization of Nodal along with multiple components and modulators of the TGF-β and Wnt signaling pathways, consistent with profoundly altered patterning cues.

Given the established role of the CCR4-NOT complex in mRNA deadenylation and turnover, we profiled the poly(A) landscape in Cnot8 knockout organoids and observed marked poly(A) tail elongation of key signaling transcripts, including Nodal.

Interestingly, transcriptomic analysis of these Brachyury-positive cells in Cnot8 KO organoids revealed signatures of notochord cells, a cell type usually absent in mammalian gastruloids.

Our screen revealed several novel regulators of germ layer differentiation, including a strong paraxial mesoderm-specific role of the CCR4-NOT component Cnot8. Loss of Cnot8 resulted in gastruloid patterning defects such as the formation of multiple Brachyury poles and aberrant growth.

Validation of our screen revealed strong global depletion of general depletion controls, while germ layer controls were selectively depleted in their respective germ layers, accompanied by the loss of characteristic transcriptomic markers.

Led by the brilliant @dadita.bsky.social‬, we first established a single-cell CRISPR screening platform in gastruloids and designed a library targeting 200 RNA-binding proteins as well as known regulators of germ layer differentiation.

The establishment of the body plan during gastrulation is a hallmark of animal life, yet much of its regulation remains unclear. Here, we combine gastruloids and single-cell CRISPR screenings to uncover new regulators of the body plan.

www.biorxiv.org/content/10.1...

Third defense this summer officially in the books. Huge congrats to Fabiola for a brilliant presentation and defense! #Summerofdefenses

….and more #gastruloid preprint with proof of how to use their robustness and scalabiliy in high throughput screens to learn about #posttranscriptional regulation of gene expression @ Sendoel and Lutolf labs www.biorxiv.org/content/10.1...

Preprint by the @sendoellab.bsky.social in collab w/ the Lutolf & Zavolan labs w/1st author David Taborsky "Regulation of mRNA polyadenylation governs mammalian body plan formation in gastruloids" @biorxivpreprint.bsky.social
buff.ly/mL3a71T
@dadita.bsky.socia
@mihaelazavolan.bsky.social

How can we identify novel regulators of germ layer differentiation and body patterning? I am happy to announce that my preprint using single-cell CRISPR screens in gastruloids to answer this question is now online! Thank you to the rest of the @sendoellab.bsky.social and all coauthors!

PhDone 🥳🎓

The last few years was full of successes, failures, ups and downs, but also full of amazing people, countless talks, great conferences, incredible science and endless support from my supervisor and my thesis committee. Thanks to all people who helped me in this amazing journey! #eIF2A

The summer of defenses continues, huge congratulations Dr. Yigit for a superbly delivered talk and an excellent defense!

Cross-tissue multicellular coordination and its rewiring in cancer - Nature Comprehensive single-cell transcriptomic analysis of 35 human tissues reveals 12 cross-tissue coordinated cellular modules that exhibit intramodule communication and dynamic changes with ageing, and w...

new out in Nature today www.nature.com/articles/s41...

The very first PhD graduate of our lab! Great science, fantastic presentation and expertly defended. Huge congratulations on this well-earned milestone Dr. Duré!

Preprint by the Sendoel Lab ( @sendoellab.bsky.social ) with first author Merve Yigit ( @merveyigit.bsky.social‬ "The alternative initiation factor eIF2A regulates 40S subunit turnover in ribosome-associated quality control"
@biorxivpreprint.bsky.social‬
buff.ly/hP9Iani
‪@anupamd.bsky.social‬

Collectively, our study identifies a new link between eIF2A and ribosome-associated quality control (RQC), implies that eIF2A promotes translation fidelity by tuning 40S ribosome rescue under stress and warrants further investigations into the role of RQC in tumorigenesis. 6/x

Finally, in lung SCC patient data, we find increased K214-RPS3 ubiquitination, the very site targeted during RQC. RNF10 and eIF2A mRNA levels both correlate with shorter overall survival, pointing to a potential link between RQC induction and tumor progression. 5/x

G3BP1–USP10 complexes rescue stalled 40S from degradation. Using dynamic SILAC in mouse and human cells, we find eIF2A KO cells have reduced 40S turnover under stress, indicating that eIF2A tunes USP10-mediated 40S rescue under stress. 4/x

Consistent with recent ribosome profiling, our 40S TCP-seq analyses reveal only a minimal role in initiation. Rather, eIF2A loss causes a marked reduction in RPS3 ubiquitination upon stalling. We demonstrate that eIF2A antagonizes USP10-mediated deubiquitination of stalled 40S subunits. 3/x

Led by the skilled @merveyigit.bsky.social, we performed TurboID-based proximity biotinylation in both homeostatic and stressed cells. Zooming into 40S interactions, we locate eIF2A near the mRNA entry channel and uncover strong interactions with G3BP1-USP10 complexes as well as RPS2 and RPS3. 2/x