Lars Velten

cell.comDesign principles of cell-state-specific enhancers in hematopoiesisScreen of minimalistic enhancers in blood progenitor cells demonstrates widespread dual activator-repressor function of transcription factors (TFs) and enables the model-guided design of cell-state-sp...

8 May 2025

Out in Cell @cp-cell.bsky.social: Design principles of cell-state-specific enhancers in hematopoiesis 🧬🩸 screen of fully synthetic enhancers in blood progenitors 🤖 AI that creates new cell state specific enhancers 🔍 negative synergies between TFs lead to specificity! www.cell.com/cell/fulltex... 🧵

It's been preprint week! Joe's great Perturb-seq story "back-to-back" with our single cell AML atlas (led by @simonhaas.bsky.social). 🤒: www.biorxiv.org/content/10.6... 🧬: www.biorxiv.org/content/10.6... These two apparently very different stories were posted back to back because of a surprise 😮🧵:

Joe Bowness@joebowness.bsky.social

Very happy to share the first pre-print from my postdoc work with @larsplus.bsky.social (which we also presented at the excellent @isehsociety.bsky.social Annual Meeting last weekend). Here we performed a CRISPRi Perturb-seq screen targeting >500 transcriptional regulators in ex vivo mouse HSPCs.

biorxiv.org| bioRxivbioRxiv - the preprint server for biology, operated by openRxiv, a nonprofit organization dedicated to advancing scientific communication

The AML story was developed completely independently of that. It dissects clinical outcomes in AML and attributes them to different biological layers - for example: relapse risk rather comes from the immune microenvironment, not the AML itself. Have a look! www.biorxiv.org/content/10.6... (5/n)

Congratulations to the first authors of both studies - @joebowness.bsky.social and Jan Barinka (from @simonhaas.bsky.social lab). I'm very priviliged to work with scientists like you. Data and code is public. (5/5)

Joe Bowness@joebowness.bsky.social

We therefore started decomposing RNA-seq datasets into program activity (wrote a small algorithm for that). When we looked at the AML atlas data, we lived a big surprise: One of our Perturb-seq programs predicts long-term survival in AML very well! Independent of genotype. (3/n)

But it didn't stop there. We found programs predicting donor age, Venetoclax response, symmetric HSC divisions... All of this suggests that programs of genetic co-regulation - only visible from perturbation experiments - are an important (and highly interpretable) layer of information. (4/n)

Joe Bowness@joebowness.bsky.social

cell.comGenome-scale perturb-seq in primary human CD4+ T cells maps context-specific regulators of T cell programs and human immune traitsA dynamic atlas of gene regulation was generated by perturbing every expressed gene across 22 million primary human CD4+ T cells under resting conditions and following re-stimulation. The resulting ma...

In perturb-seq, Joe identified "gene regulatory programs". These are groups of genes that share common regulators - not co-expression programs. This nicely grouped genes into pathways. So we asked: are these genes sets any useful? (2/n)

Lars Velten reposted

Jonathan Pritchard

@jkpritch.bsky.social

29 Aug

Genome-scale perturb-seq in human T cells. Our fantastic postdocs @ronghuizhu.bsky.social and @emmamarydann.bsky.social have done great work here to show the power and opportunities of perturb-seq in primary cells. This is part of a wonderful long-term collaboration with @marsonlab.bsky.social

Emma Dann@emmamarydann.bsky.social

Our work on systematic perturb-seq of primary human T cells is now out in Cell 🎉 www.cell.com/cell/fulltex... It's been a privilege to work with @ronghuizhu.bsky.social between @jkpritch.bsky.social @marsonlab.bsky.social labs, with a dream-team of co-authors ❤️ Highlights in preprint thread👇

doi.orgCumulative transcription factor binding and p300-mediated histone acetylation drive enhancer activation frequency - Nature GeneticsThis study uses single-molecule footprinting to quantify chromatin accessibility at enhancers and promoters in mouse embryonic stem cells and to dissect the contributions of transcription factor bindi...

17 Aug

Wow! Not sure why this appears in my feed now but what an interesting story! Congrats @gabaldonlab.bsky.social

BIST-Barcelona Institute of Science and Technology@bist.eu

🦠 How did our cells originate? A study by @gabaldonlab.bsky.social at @irbbarcelona.org & @bsc-cns.bsky.social suggests cellular complexity emerged gradually over millions of years, rather than from a single evolutionary event. 📝 Published in @nature.com #BISTCommunity 👉 bist.eu/a-study-by-i...

Lars Velten reposted

Arnaud Krebs

@arnaudkr.bsky.social

12 Aug

How many TFs to you need to open chromatin at enhancers? Very excited to see this one out! Check out the augmented version with combinatorial motif mutant libraries in Figure 5! Very proud of @guidobarzaghi.bsky.social @valentinabaderna.bsky.social @embl.org

Guido Barzaghi@guidobarzaghi.bsky.social

📄 That's a wrap 📄 we're excited to share that the latest from @arnaudkr.bsky.social 's lab and Judith Zaugg's lab is at last online at doi.org/10.1038/s415.... Many thanks to my co-first @valentinabaderna.bsky.social and to @embl.org for the wonderful research environment.

link.springer.comLentiviral single-cell MPRA of synthetic enhancers reveals motif affinity-based encoding of cell state specificity - Genome BiologyBackground Cell state-specific gene expression programs emerge from the interplay between cis-regulatory elements (CREs), such as enhancers, and transcription factors (TFs). Massively parallel reporte...

@juruehle.bsky.social's PhD work is now out in Genome Biology 📚🧬 : Lentiviral single-cell MPRA of synthetic enhancers reveals motif affinity-based encoding of cell state specificity link.springer.com/article/10.1186/s13059-026-04186-9 Julia achieved three cool things with this work...🧵

2. Biology: Low affinity transcription factor binding sites respond linearly to changes in TF concentration whereas high affinity sites are saturated. Enhancers with high affinity sites are therefore rather regulated by co-factor availability!

3. And the best: Julia really pulled this project through from start to end. I was *very* hands-off here - makes me look old, but huge congrats to Julia on a great PhD and good luck for your next steps🇨🇭!

addgene.orgAddgene: pLS-hu6-EGFP-sc-lentiMPRAPlasmid pLS-hu6-EGFP-sc-lentiMPRA from Dr. Lars Velten's lab is published in Genome Biol (2026) This plasmid is available through Addgene.

1. Technology: The first lentiviral assay to screen enhancer function with single cell resolution in primary cells 🦠. Relevant to developers of gene therapy, gene regulation aficionados and synthetic biologists alike - plasmid is on addgene www.addgene.org/257694/

Lars Velten reposted

Annique Claringbould

@anniquec.bsky.social

12 Mar

🧬 How do immune disease-relevant variants affect gene regulatory networks in CD4+ T cells? 🧪🖥️ We coupled two large-scale CRISPRi screens (>4M cells) to map the downstream cascades of thousands of SNPs More details in the thread below 👇 or in the article 📖 on biorxiv tinyurl.com/CD4screens

4 Mar

Now, synthetic enhancers with single cells - great work by @juruehle.bsky.social : www.biorxiv.org/content/10.6...

Lars Velten@larsplus.bsky.social

Alejo Rodriguez-Fraticelli

4 Mar

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 👀

Julia Rühle@juruehle.bsky.social

The main project of my PhD 🧬🔬 is out: we developed single-cell lentiMPRA, a lentivirus-based method to measure enhancer activity and transcriptomes at single-cell resolution. We then applied sc-lentiMPRA to fully synthetic enhancers 🧩... 🔗 doi.org/10.64898/202...

doi.orgdoi.org

Lars Velten reposted

@alejofraticelli.bsky.social

27 Feb

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

nature.comCharting single-cell lineages with synthetic and natural barcodes - Nature Reviews GeneticsIn 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...

27 Feb

Insightful seminar by Roderic Guigó: Figure 1 of the Craig Venter human genome paper (Science, 2001) was made by a Spanish PhD student who had no salary and earned his living serving tables in a Pizzeria.

Centre de Regulació Genòmica (CRG)@crg.eu

Exactly 25 years ago, @rodericguigo.bsky.social and his PhD student published the first draft of the human genome in Science. The Catalan researchers were the only two from all Spain that took part. Here they are reflecting on the huge scientific feat: www.crg.eu/en/news/25-y...

27 Feb

Expansion cultures of mouse AML stem cells! Enabling large scale genetic screens in a system that's very close to "the real thing", with deep implications for drug discovery. Great work @alejofraticelli.bsky.social and @indrasingh.bsky.social

Alejo Rodriguez-Fraticelli@alejofraticelli.bsky.social

🚨 NEW @FraticelliLab PREPRINT JUST WENT LIVE biorxiv.org/content/10.6... Here, we describe PLSTCs, Soluplus-based expansion cultures of primary mouse *Acute Myeloid Leukemia* Stem Cells. And then we use LARRY barcoding to identify drivers of leukemogenicity and drug resistance!

@brittavelten.bsky.social

17 Feb

Early bird registration is closing Feb 28! We will have an AMAZING party!

Lars Velten@larsplus.bsky.social

ISCO (Innovations in Single-Cell OMICS) will be back in beautiful Barcelona! 🗓️ 28th/29th of May 2026 📍Barcelona Biomedical Research Park @prbb.org (beachfront!) Keynotes: @bartdeplancke.bsky.social and @bocklab.bsky.social Submit your abstract and present your research! www.isco-conference.eu

Lars Velten reposted

Vijay G. Sankaran

@bloodgenes.bsky.social

2 Jan

Delighted to have our work on 🧬 resilience to 🩸cancer led by @g-agarwal.bsky.social & amazing collaborators, including @kharaslab.bsky.social, published in @science.org: www.science.org/doi/10.1126/... 🧵

Lars Velten reposted

Britta Velten

3 Dec 2025

Happy to see this out now in Cell Genomics: A genome-scale single-cell CRISPRi map of trans gene regulation across human pluripotent stem cell lines: www.cell.com/cell-genomic...

cell.comA genome-scale single-cell CRISPRi map of trans gene regulation across human pluripotent stem cell linesFeng et al. present the first genome-scale CRISPR interference perturbation map with scRNA-seq readout across many genetic backgrounds in human pluripotent cells, pioneering population-scale CRISPR pe...

5 Dec 2025

@yusufroohani.bsky.social @rberrens.bsky.social @timcoorens.bsky.social @hsiuchuanlin.bsky.social @albarmeira.bsky.social @ferrannadeu.bsky.social @alejofraticelli.bsky.social @elimereu.bsky.social @simonhaas.bsky.social @leifludwig.bsky.social @stefaniegrosswendt.bsky.social

5 Dec 2025

Christoph Bock Lab @ CeMM & MedUni Vienna

20 Nov 2025

We are looking for a postdoc to join our team! If you're interested in translating a cutting edge genomics technology (www.nature.com/articles/s41...) to real-life applications in hematology, this is for you. We offer a unique working environment ON THE BEACH: recruitment.crg.eu/content/jobs...

Lars Velten reposted

@bocklab.bsky.social

11 Nov 2025

🗨️ Just published in Nature Biotechnology: Our CellWhisperer AI enables chat-based analysis of single-cell sequencing data. You can talk to your cells & figure out the biology without writing any computer code. Paper here: www.nature.com/articles/s41.... Annotated walkthrough in a thread below (1/11)

Lars Velten reposted

Centre de Regulació Genòmica (CRG)

@crg.eu

23 Oct 2025

Are you looking for a PhD? Join us in Barcelona! You'll dive into a community of >100 PhD students from 30 countries exploring the frontiers of biology. You can also join an online workshop on 6 November (15:00 CET) to learn how to find the right lab for you. More info: www.crg.eu/en/content/t...

Lars Velten reposted

Dan Landau

@landau.bsky.social

14 Oct 2025

Big, beautiful trees!! SMART-PTA for whole-genome+transcriptome on thousand of single cells from the normal human esophagus 🤯 Massively scaling up the power of scWGS to build deep phylogenies and chart somatic evolution from birth throughout life. www.biorxiv.org/content/10.1...

Lars Velten reposted

Max-Planck-Gesellschaft

@maxplanck.de

15 Sept 2025

Early-career researchers: want to run your own lab? 🌟Max Planck Research Groups offer 6+ years, up to €2.7M in funding, open-topic freedom, team support & tenure-track opportunities. Intrigued? 😃Apply by Oct 14, 2025! www.mpg.de/max-planck-r...

18 Sept 2025

This was a lot of fun! Thanks Daylon and @arunsharmaphd.bsky.social for being great hosts!

Stem Cell Podcast@stemcellpodcast.com

We have a new episode out! Dr. Lars Velten from the Centre for Genomic Regulation talks about his research on #LineageTracing and #hematopoiesis: https://bit.ly/4gsvo5X

economist.comIs the decline of reading making politics dumber?As people read less they think less clearly, scholars fear

7 Sept 2025

www.economist.com/culture/2025... To counter this, here’s my 3 fav reads 📚 from this summer: - The dream of the Celt by Mario Vargas Llosa - Paradise by Abdulrazak Gurnah - Dzhamilia by Tsjyngyz Ajtmatov

nature.comFunctional phenotyping of genomic variants using joint multiomic single-cell DNA–RNA sequencing - Nature MethodsThis study introduces SDR-seq, a droplet-based single-cell DNA–RNA sequencing platform, enabling the study of gene expression profiles linked to both noncoding and coding variants.

2 Sept 2025

New method from my former lab - combining targeted RNA-seq and DNA-seq from the same cell on the @missionbio.bsky.social platform. Congrats! It can also be combined with targeted methylation profiling and clonal tracing. www.nature.com/articles/s41...

nature.comUltra-high-scale cytometry-based cellular interaction mapping - Nature MethodsInteract-omics, a high-throughput cytometry-based framework, resolves the cellular interaction landscape.

13 Aug 2025

A really powerful, easy and affordable method for profiling cellular interactions in the immune system. Congrats @dom60.bsky.social , @simonhaas.bsky.social and everyone involved!

Dominik Vonficht@dom60.bsky.social

Excited to share the latest publication from my PhD with @simonhaas.bsky.social at @dkfz.bsky.social, out now in Nature Methods! A big thanks to all co-authors, especially Lea Jopp-Saile, Schayan Yousefian and @viktoriaflore.bsky.social for all their hard work. www.nature.com/articles/s41...

Lars Velten reposted

Constantin Ahlmann-Eltze

@const-ae.bsky.social

4 Aug 2025

Our paper benchmarking foundation models for perturbation effect prediction is finally published 🎉🥳🎉 www.nature.com/articles/s41... We show that none of the available* models outperform simple linear baselines. Since the original preprint, we added more methods, metrics, and prettier figures! 🧵

cell.comIterative deep learning design of human enhancers exploits condensed sequence grammar to achieve cell-type specificityYin et al. demonstrate the use of iteratively retrained deep learning models to design synthetic enhancers for progressively higher cell-type specificity. They show the feasibility of model training f...

15 July 2025

Interesting piece on automated enhancer design from the Seelig lab: www.cell.com/cell-systems...

23 June 2025

Congrats @hoheyn.bsky.social , @lgmartelotto.bsky.social and team!

Waggoner Lab@labwaggoner.bsky.social

STAMP: Single-cell transcriptomics analysis and multimodal profiling through imaging @cellcellpress.bsky.social @lgmartelotto.bsky.social @hoheyn.bsky.social www.cell.com/cell/fulltex...

cadenaser.com"A partir de los 50 casi todas las células madre se llaman Rodríguez" (Y eso es malo)Un estudio liderado por dos centros de investigación de Barcelona ha descubierto que, a partir de esa edad, cada vez tenemos menos células madre sanguíneas y las que hay se replican cada vez con más e...

Thanks to phenomenal work by @crg.eu and @irbbarcelona.org press offices, we got to communicate our findings on 🧬 methylation barcodes and 🩸 blood ageing to a wide audience. A cool experience! 🧵 with highlights in 5 languages and funny moments 😬😅 cadenaser.com/nacional/202... (1/n)

antena3.comCientíficos españoles descubren cómo envejece la sangre: un gran hallazgo para la lucha contra la leucemia y el envejecimientoUn estudio desarrollado en Barcelona ha dado con la clave para entender cómo envejece la sangre. El hallazgo podría facilitar la detección temprana de enfermedades como la leucemia y abrir nuevas vías...

😵‍💫: Private TV antenna3 hectically shot an interview 1.5h before their 3pm news, got a lot wrong (no we did not rejuvenate mice by ablating old stem cells, Irv Weissman did that) BUT they made us the good news of the day and it's somehow funny www.antena3.com/noticias/cie...

ft.comScientists make breakthroughs on blood ageing and limb regrowthTwo new studies could help develop better therapies for rejuvenation and regeneration

🇬🇧: Finally, English-language coverage by Financial Times, a small London-based newspaper 😉. Thanks again @omarjam.bsky.social and Nahia (@irbbarcelona.org) for making all this possible! www.ft.com/content/a1f8...

lemonde.frDès l’âge de 50 ans, les cellules de notre sang s’appauvrissentUne équipe espagnole a retracé l’évolution des lignées de cellules du sang chez 13 personnes de 35 à 70 ans. A partir de la cinquantaine, le nombre de cellules souches capables d’engendrer des cellule...

🇫🇷: @scherermich.bsky.social was brave enough to speak to @lemonde.fr in French 💪! Excellent article that definitely sticks out with the accompanying visual. www.lemonde.fr/sciences/art... (6/n)

😬: SER Catalunya, most-listened radio around here, interviewed me at 8:40 (instead of 8:50)... they reached me in the elevator, put me live on air and started asking in Catalan. Had to guess what they meant and improvise. The good thing, I was awake after this 😅 (can't upload audio to bsky - 7/n)

😅: "From age 50 almost all stem cells are called Rodriguez (and that's bad)". All credit for this to @alejofraticelli.bsky.social - family names are a fantastic analogy to explain clonal processes cadenaser.com/nacional/202... (4/n)

science.orf.at„Blutbarcodes“ könnten Alterung verlangsamenAuch das Blut altert: Ab 50 Jahren verringert sich die Vielfalt der Stammzellen, die Blut produzieren. Ein Forschungsteam hat nun ein „Barcodesystem“ entwickelt, das die verschiedenen Blutstammzellen ...

🇦🇹: Austrian ORF covered both the blood ageing context and the DNA methylation discovery in two minutes on the radio after interviewing @martinabraun.bsky.social and me. Real quality science journalism. science.orf.at/stories/3230... (5/n)

doi.orgClonal tracing with somatic epimutations reveals dynamics of blood ageing - NatureThe discovery that DNA methylation of different CpG sites can serve as digital barcodes of clonal identity led to the development of EPI-Clone, an algorithm that enables single-cell lineage tracing th...

First of all, here's the science, in case you missed it. bsky.app/profile/lars... Now come the media highlights (2/n)

Lars Velten@larsplus.bsky.social

Out @nature.com: Clonal tracing with somatic epimutations 🧬 Single cell methylome encodes cell state & clonal identity 🔨 EPI-Clone reads out both (+mutations, +RNA) at scale 🩸 Clonal expansions of HSCs are universal from age 50, not driven by CH mutations doi.org/10.1038/s415... 🧵