iiinova — where your digital self keeps evolving

Reposted by Sergi Cuartero

Noelia Díaz @noeliadiaz.bsky.social · 24/04/2025

🚨Want to get hands-on experience on low input chromatin techniques? Join us at the @EPIBOOST22 Chromatin Explorer Summer School this July in sunny Barcelona 🧬🥼🖥️🐟☀️🏖️ ℹ️: tinyurl.com/bdzbt36z 🎯Register here: forms.gle/mBA1gkEkYrYh... 📆Application deadline: 19th May 2025

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Sergi Cuartero @scuartero.bsky.social · 14/04/2025

12/ So thankful to everyone who made this possible — Maria for leading the project; the bioinformaticians Gerard Martínez-Cebrián and Lucía Lorenzi; and all our collaborators and funding agencies!🙏🙏🙏

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Sergi Cuartero @scuartero.bsky.social · 14/04/2025

11/ Indeed, p30-expressing cells were more sensitive to ER stress — revealing a potential vulnerability in CEBPA-mutant AML

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Sergi Cuartero @scuartero.bsky.social · 14/04/2025

10/ Surprisingly, co-IPs revealed that p30 fails to interact with ATF4, while p42 does — impairing downstream signaling. Given ATF4’s key role in the ER stress response, we tested how p30 cells respond to tunicamycin-induced stress

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Sergi Cuartero @scuartero.bsky.social · 14/04/2025

9/ We then turned to another AP-1 factor: ATF4, whose binding motifs were enriched in p30-downregulated enhancers. ATF4 itself wasn’t downregulated, but its binding sites were less active — why?

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Sergi Cuartero @scuartero.bsky.social · 14/04/2025

8/Zooming in, p30-expressing cells failed to activate interactions between the FOS gene and nearby regulatory regions. Also, forced FOS expression rescued some of the downstream transcriptional programs and partially restored inflammatory fitness

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Sergi Cuartero @scuartero.bsky.social · 14/04/2025

7/ H3K27ac ChIP-seq revealed many differentially active enhancers, and these were enriched for AP-1 motifs. We analyzed expression of the major AP-1 members and noticed that FOS and its paralogs were consistently downregulated in all our experimental models

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Sergi Cuartero @scuartero.bsky.social · 14/04/2025

6/ Still, p30 binds chromatin and is transcriptionally active — so why the defective inflammatory response? ChIP-seq of both isoforms showed similar binding on inflammatory genes. Was there something else?

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Sergi Cuartero @scuartero.bsky.social · 14/04/2025

5/This had a protective effect: since prolonged inflammation can be detrimental to hematopoietic progenitors, expressing p30 instead of p42 conferred resistance to inflammatory stress

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Sergi Cuartero @scuartero.bsky.social · 14/04/2025

4/How does this affect the inflammatory response? Upon LPS stimulation, p30 cells failed to robustly activate early response genes, though late responses were less affected.

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Sergi Cuartero @scuartero.bsky.social · 14/04/2025

3/ Was this just a mouse-specific effect? Not at all. RNA-seq from CEBPA-mutant AML patients confirmed the same: a marked reduction in inflammatory gene expression. And when we reintroduced p42 into mutant AML cells, it partially rescued inflammatory gene expression.

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Sergi Cuartero @scuartero.bsky.social · 14/04/2025

2/Using undifferentiated and differentiated mouse primary cells and an inducible HSC line, we found that p30 cells showed a strong downregulation of inflammatory genes compared to p42 cells — and this wasn’t due to differences in maturation.

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Sergi Cuartero @scuartero.bsky.social · 14/04/2025

1/Mutations in CEBPA, a key myeloid transcription factor, are common in AML. Very often these mutations result in the expression of a shorter isoform (p30) instead of the full-length p42. But what are the transcriptional consequences of expressing p30 instead of p42?

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Sergi Cuartero @scuartero.bsky.social · 14/04/2025

Extremely happy to share that the first paper from our lab is now published! Driven by the very talented PhD student Maria Cadefau, we studied how CEBPA mutations shape transcriptional programs in AML. A thread 🧵👇 www.nature.com/articles/s41...

nature.com

Mutant CEBPA promotes tolerance to inflammatory stress through deficient AP-1 activation - Nature Communications

CEBPA is frequently mutated in acute myeloid leukemia (AML), but the transcriptional impact of the AML-associated isoform remains unclear. Here, the authors show that CEBPA-mutant cells have reduced i...

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Reposted by Sergi Cuartero

elvinwag.bsky.social @elvinwag.bsky.social · 08/04/2025

Thrilled to share the first pre-print from our lab! We tackled a big question: Why are some pediatric leukemias extremely aggressive? We explored the developmental origins of fusion-driven acute myeloid leukemia (AML). Let's dive in! #AML #NUP98 A thread... n/13

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Reposted by Sergi Cuartero

Barriga Lab VHIO @barrigalabvhio.bsky.social · 26/11/2024

Hi! I just compiled some of the new Barcelona cancer labs! Many more missing, so let me know if anyone needs to be added! go.bsky.app/AkCGugm

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Reposted by Sergi Cuartero

Felix Weiss @fweiss.bsky.social · 19/11/2024

Happy to share that I recently joined the editorial board of Cell Death & Differentiation! The scope of the journal is expanding and we encourage submission from a broad range of immunology related topics, not just your favourite -tosis 😄 Link to journal below: www.nature.com/cdd/

nature.com

Cell Death & Differentiation

Cell Death & Differentiation is a journal devoted to the cell biology, molecular biology and biochemistry of cell death, survival, stemness and ...

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Reposted by Sergi Cuartero

Esteban Ballestar @eballestar.bsky.social · 17/11/2024

Do not miss the chance to make a difference as #ProjectManager of the #IMMERGE #DoctoralNetwork institut-josep-carreras-ijc.jobs.personio.com/job/1796149?...

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