Alejo Rodriguez-Fraticelli

Pls re-post: My department @oxfordbiochemistry.bsky.social are recruiting for several new faculty positions (links below). Broad search in molecular biology/biochemistry, across prokaryotes and eukaryotes. Interested in understanding life at the molecular level, this job might be for you!
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It’s seriously impressive! Now that I’m reading it more in detail, I’m obsessed with this mechanism! So cool! Looking forward to celebrating soon!

Amazing work Maria!!! Congrats!!!

Proud of @juruehle.bsky.social for getting her PhD paper on biorxiv! In it, we take synthetic enhancer screens to the single cell level, offering new insight into how transcription factors and enhancers interact 👀

Preprint Editors – Development's next step into the preprint landscape Summary: This Editorial announces a call for Preprint Editors in Development to help expand the journal's relationship with preprints by curating our ‘In preprints’ articles.

New from @dev-journal.bsky.social: we're launching a new initiative and hiring Preprint Editors to help navigate the growing world of preprints in developmental & stem cell biology

Join our community & shape the future of research

journals.biologists.com/dev/article/...

Absolutely loved it Thibaut. Mega congrats!!! What a story.

I still remember to this day how much this specific day, the day the genome draft was published, pushed me into choosing to study life sciences… it was a breakthrough moment for so many young kids. 25 years, wow.

Dot is unreal. I think I was completely unaware that editors could have such super-powers. I will never look at an editor job the same way ever gain.

👏🏻👏🏻👏🏻

Big thanks to amazing (absolutely amazing) editor
Dorothy Clyde and to reviewers @timcoorens.bsky.social and Show-wen Wang!!!! Your input and comments were absolutely crucial! Thanks for pushing us to make it the best we could.

Charting single-cell lineages with synthetic and natural barcodes - Nature Reviews Genetics In this Review, Rodriguez-Fraticelli and Parreno discuss advances in single-cell lineage-tracing methods and how their application to diverse biological processes, such as development, ageing and canc...

INTERESTED IN SINGLE-CELL LINEAGE TRACING?

Check our new review @naturerevgenet.bsky.social from the @alejofraticelli.bsky.social lab 🎉🎉

nature.com/articles/s41...

With Victoria Parreno, we tried to update the modern manual for genetic tracing and clonal analysis.

Read link: rdcu.be/e50gy

📢 The 5th edition of #ISCO – Innovation in #SingleCell #Omics is almost here!

🗓 28–29 May 2026
📍 @prbb.org 
🚨 Early-bird deadline: 28 Feb

Register: https://www.isco-conference.eu/

@crg.eu @carrerasijc.bsky.social @alejofraticelli.bsky.social

Leukemia stem cell expansion cultures reveal clonal drivers of leukemogenesis and therapy response https://www.biorxiv.org/content/10.64898/2026.02.24.707683v1

Finally, and most crucially, I want to thank the funding from
Cris Cancer Foundation, who believed that it was possible to transform cancer research with my crazy ideas.
And also @erc.europa.eu and @ageinves.bsky.social
for supporting our high-risk high-gain ideas.

I want to finish by acknowledging the support of
@irbbarcelona.org and @icreacommunity.bsky.social, one of the best institutes for biomedical research in Europe, and the amazing team of people working there, from #corefacilities to #administration, because they truly made this project a reality.

We are now making PLSTC LSCs with other mutations, and modifying them (almost like a cell line) to perform experiments that seemed crazy just a few months ago (knock-ins, knock-outs, etc.). The genetic engineering possibilities may be endless. Get in touch if you'd like to set them up in your lab!

Of course, this is one of those studies that offers more questions than answers, and we're quite happy with this! We believe PLSTCs can pave the way to accelerate discovery of novel targets to treat these aggressive leukemias.

In sum, we believe that LSCs can occupy a wide variety of LSC-like states, with certain primitive-like states primed with expression of MegE genes and biased towards self-renewal. These states are somehow dependent on CS proteoglycans (Csgalnact1) and may be targeted by chABC.

Validating the CRISPR data, chABC treatment significantly delayed leukemia initiation. And, more importantly, it synergized with chemotherapy, making it harder for LSCs to come back after chemotherapy treatment (after drug washout).

Csgalnact1 is the main enzyme responsible of initiating polymerization of chondroitin sulfate chains. Chondroitin-sulfate proteoglycans are main drivers of fibrosis in injury. Importantly, there is a therapy under research, Chondroitinase ABC, that can target this mechanism.

Leveraging these LSC-enriched PLSTC cultures, we used a CROPseq strategy (pioneered by @bocklab.bsky.social) to identify regulators for various LSC states. We identified Csgalnact1 as a potential novel regulator (and we also rediscovered Gapdh and Adgrg1/GPR56!).

Next, modeling induction chemotherapy in vivo, we found that some LSC-biased clones tend to be more resistant, and these express higher levels of the megakaryocytic/erythroid markers. Shockingly, after therapy, these clones move to the spleen, and reinforce their megakaryocytic-erythroid flavor!!!

Surprsingly, just like in normal HSCs, we find that there are LSC-biased clones, that have a preference for self-renewal and produce little mature AML progeny!!! These clones seem to express many markers of megakaryocytic-erythroid MPPs.

In vivo, as reported by Huntly, Levine, and others, there is a wider variety of fate behaviors as these LSCs differentiate into different mature-like trajectories (all with some degree of monocytic progenitor differentiation, which is a hallmark of these AMLs).

Some specific clonotypes appear to be hyper efficient at engraftment (LSC-3 group), though all could engraft at some rate. Using state-fate LARRY to select the most leukemogenic state, we find markers of Multipotent progenitors, but with HSC-like cell adhesion/ECM modules.

Tracing clonality, we find that PLSTC LSCs occupy a variety of stable, self-renewing states within the same well. So, this apparent continuum is actually made of thousands of clonal "constellations"!!!! Using @adameykolab.bsky.social super cool tool scLiTr, we can group these into 5 fate clusters.

And, importantly, PLSTCs can be modified, selected, frozen, thawed, etc. just like a cell line (protocol paper will be submitted separately soon!).

Of course, we thought this was a great opportunity to understand AML LSC clonal complexity. ENTER LARRYv3!

Compared to classic StemSpan cultures, PLSTCs are highly sensitive to metabolic therapy (Venetoclax), and resistant to conventional chemotherapy (araC/Doxo), highlighting similarities with primitive leukemic cell states.

And they found them. We call these PLSTCs ("Polymer-based Leukemia STem cell Cultures"). PLSTCs show a remarkable capacity to expand highly potent, primitive LSCs even after months in culture (with AML initiation in 20-30 days at < 100 cell doses).

Indra Singh @indrasingh.bsky.social led the project at the end of his PhD, and then it was taken to the finish line by postdoc Andrea Polazzi. This killer team took the challenge to find the most pure culture reagents to maintain aggressive AML LSCs, inspired by Wilkinson and Yamazaki labs.