Clonal expansions can remodel entire tissues even when they appear normal, but what mechanisms drive this? And how do these processes differ from tumorigenesis? Out @Nature, we identify distinct TNF programs during tumor evolution. 🧵 https://t.co/S3w9Zl1NE2

Again, with the essential use of sibling controls, in a nationwide prospective study in Sweden of ~2.5 million children, no increased risk even with higher dose exposure https://t.co/3DNKf4vfVf Let's talk about "gold standard science"

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!

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 key 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 T/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. Cnot8 KO led to gastruloid patterning defects such as the formation of multiple T 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 @DavidTaborsky6 , 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. https://t.co/FeJph9npLq

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

📢 Last chance to register! There's still time to sign up for the FUSION Stem Cells and Cancer Conference 🗓️ Registration closes on 31st July https://t.co/oWSvj6jXiW Co-chairs @JonesLabUCSF @PlathLab @KateMiro1

….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 @oncodaily and @TheLutolfLab https://t.co/9DCGW1yiOv

One Month to Go!🚨 Countdown for the STEM CELLS & CANCER Fusion Conference — a unique gathering of global leaders sharing their ground breaking research. 🧬Ignite new ideas by Mediterranean Sea-Malta 🏝️ 📅Final Deadline: 31 July 🎤Unmissable speakers...🧵 https://t.co/oWSvj6jXiW

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

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

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