Sendoel Lab
@sendoellab.bsky.social
Sendoel lab at the University of Zurich, alumnus of the The Rockefeller University, NYC.
We are excited about mRNA translation, stem cells and cancer.
www.sendoellab.org
We are excited about mRNA translation, stem cells and cancer.
www.sendoellab.org
The summer of defenses comes to an end! Huge congratulations to David (@dadita.bsky.social ) on a brillant PhD and thank you for everything you have done to shape our lab community from day 1 on. We’re thrilled you’re staying in Zurich and wish you all the best in your next chapter!
October 31, 2025 at 9:52 AM
The summer of defenses comes to an end! Huge congratulations to David (@dadita.bsky.social ) on a brillant PhD and thank you for everything you have done to shape our lab community from day 1 on. We’re thrilled you’re staying in Zurich and wish you all the best in your next chapter!
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!
Wishing you all the best in your next chapters, we’re excited to see what comes next for you!
September 2, 2025 at 3:55 PM
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!
Wishing you all the best in your next chapters, we’re excited to see what comes next for you!
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.
August 6, 2025 at 4:14 PM
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.
August 6, 2025 at 4:14 PM
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.
August 6, 2025 at 4:14 PM
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.
August 6, 2025 at 4:14 PM
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.
August 6, 2025 at 4:14 PM
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.
August 6, 2025 at 4:14 PM
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.
August 6, 2025 at 4:14 PM
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.
August 6, 2025 at 4:14 PM
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.
August 6, 2025 at 4:14 PM
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...
www.biorxiv.org/content/10.1...
August 6, 2025 at 4:14 PM
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...
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
August 4, 2025 at 3:03 PM
Third defense this summer officially in the books. Huge congrats to Fabiola for a brilliant presentation and defense! #Summerofdefenses
The summer of defenses continues, huge congratulations Dr. Yigit for a superbly delivered talk and an excellent defense!
June 27, 2025 at 5:07 PM
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!
May 28, 2025 at 2:37 PM
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
May 26, 2025 at 9:35 PM
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
May 26, 2025 at 9:35 PM
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
May 26, 2025 at 9:35 PM
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
May 26, 2025 at 9:35 PM
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
May 26, 2025 at 9:35 PM
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
Our findings suggest that Gm10076 acts as a second Rpl41 source, explaining mild effects of Rpl41 loss. Knocking down Rpl41 in Gm10076 mutants almost fully halted proliferation. Thus, although RPL41 has been considered non-essential, this intersubunit bridge protein is in fact critical. 8/9
March 19, 2025 at 4:01 PM
Our findings suggest that Gm10076 acts as a second Rpl41 source, explaining mild effects of Rpl41 loss. Knocking down Rpl41 in Gm10076 mutants almost fully halted proliferation. Thus, although RPL41 has been considered non-essential, this intersubunit bridge protein is in fact critical. 8/9
We observed a 40% reduction in overall protein synthesis in Gm10076 mutant keratinocytes. Ribosome profiling and RNA-seq revealed broad changes in the translational landscape, indicating that Gm10076 may contribute significantly to total cellular RPL41 levels. 7/9
March 19, 2025 at 4:01 PM
We observed a 40% reduction in overall protein synthesis in Gm10076 mutant keratinocytes. Ribosome profiling and RNA-seq revealed broad changes in the translational landscape, indicating that Gm10076 may contribute significantly to total cellular RPL41 levels. 7/9
We identified Gm10076 perturbation as the top depleted hit. This 25-amino-acid microprotein, encoded on the Gm10076 lncRNA, fully matches the RPL41 protein sequence, suggesting the existence of a second Rpl41 gene and prompting us to explore its role at the intersubunit bridge of the ribosome.6/9
March 19, 2025 at 3:44 PM
We identified Gm10076 perturbation as the top depleted hit. This 25-amino-acid microprotein, encoded on the Gm10076 lncRNA, fully matches the RPL41 protein sequence, suggesting the existence of a second Rpl41 gene and prompting us to explore its role at the intersubunit bridge of the ribosome.6/9
We then validated 29 microproteins in a secondary screen both in vivo and in vitro, resulting in a high-confidence list of candidate microproteins that consistently displayed the same phenotype. 5/9
March 19, 2025 at 3:44 PM
We then validated 29 microproteins in a secondary screen both in vivo and in vitro, resulting in a high-confidence list of candidate microproteins that consistently displayed the same phenotype. 5/9
Notably, a cohort of 14 microprotein perturbations induced substantial transcriptional changes across the major epidermal cell types, suggesting that this subset of microproteins globally shapes gene expression and cellular function. 4/9
March 19, 2025 at 3:44 PM
Notably, a cohort of 14 microprotein perturbations induced substantial transcriptional changes across the major epidermal cell types, suggesting that this subset of microproteins globally shapes gene expression and cellular function. 4/9