Jeroen Guikema

Single-cell nascent transcription reveals sparse genome usage and plasticity scFLUENT-seq is a single-cell method that sensitively captures nascent nuclear transcriptomes to reveal mRNA and ncRNA dynamics, heterogeneity across chromatin compartments, and transcriptional divers...

"Surprisingly, individual cells—from splenic lymphocytes to pluripotent stem cells—transcribe only ∼0.02%–3.1% of the genome, versus >80% in bulk, revealing limited genome engagement and profound cell-type and cell-to-cell heterogeneity"

www.cell.com/cell/abstrac...

Do you know how badly things have to be going in America for us to be owned this hard by the Dutch? The Dutch of all people

What makes genes burst Genes burst. Instead of being monotonously transcribed by a steady stream of RNA polymerases, active genes undergo transient and random pulses of transcription that are referred to as gene bursting. This property is ubiquitous and evolutionarily conserved from bacteria to humans, and reflects the inherent stochastic nature of most biological processes. The frequency and duration of gene busting events varies greatly between genes and is now recognized to be controlled by an intricate interplay between transcription factors, chromatin features, and the transcription machinery. Recent findings also point to proximal regulation of bursting by epigenetic chromatin states, a novel role of non-histone modifications, and of distal control of bursting patterns by enhancers. Uncovering the regulatory mechanisms of gene bursting sheds light on how cells maintain a diverse range of gene-specific expression by modulating the different kinetic parameters of bursting.

What makes genes burst

APE1 active site residue Asn174 stabilizes the AP-site and is essential for catalysis Apurinic/Apyrimidinic (AP)-sites are common and highly mutagenic DNA lesions that can arise spontaneously or as intermediates during Base Excision Repair (BER). The enzyme apurinic/apyrimidinic endonu...

Thrilled to share our lab’s latest work in JBC! 🎉 We uncovered a critical role for APE1 Asn174 in stabilizing AP-sites using mutagenesis, enzymology, crystallography, and MD-simulations. Congrats to Kaitlin Dehart and all the co-authors! Check it out: www.jbc.org/article/S002...

Excised DNA circles from V(D)J recombination promote relapsed leukaemia Nature - Excised signal circles are circular DNA by-products of V(D)J recombination that form a complex with the V(D)J recombinase, and when increased in abundance, result in increased mutagenesis,...

Excised DNA circles from V(D)J recombination promote relapsed leukaemia

Cutting your own DNA has a risk of leukaemia.

www.nature.com/artic...
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Pospelova et al. present a comparative analysis of adaptive immune loci across diverse mammalian species, uncovering relationships between locus architecture, characteristics of immune genes, and population dynamics. The artwork illustrates how the structure of immunoglobulin heavy chain loci influences gene variability in three representative species from the study – the mountain lion, the ring-tailed lemur, and European hedgehog.

Pospelova et al. present a comparative analysis of full-length sequences of IG/TR loci across 46 mammalian species, demonstrating these as rapidly evolving genomic regions, with implications for immunogenomics.

🔗 doi.org/10.1093/molbev/msaf152

#evobio #molbio

Respiratory viral infections awaken metastatic breast cancer cells in lungs Nature - Mouse models show that respiratory infections from viruses such as influenza and SARS-CoV-2 can trigger metastasis of dormant breast cancer cells in the lungs, a finding supported by...

Respiratory viral infections awaken metastatic breast cancer cells in lungs

Note: This concerns many infections (inflammation, trauma), including respiratory viruses and is NOT specific for SARS-CoV-2 as some claim.

www.nature.com/artic...
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Quantitative measurement of phenotype dynamics during cancer drug resistance evolution using genetic barcoding - Nature Communications Understanding the dynamics of how drug resistance originates in cancer remains crucial, but it is not possible to observe them directly. Here, the authors construct a mathematical framework to infer d...

Using barcodes 📊 to track cancer 💊 resistance evolution: is it clonal selection or plasticity? @fwhiting.bsky.social‬ knows! His new "Evolutionary Informed Resistance Assays" (EIRAs) framework infers resistance evolution dynamics from barcode diversity data. www.nature.com/articles/s41... @icr.ac.uk

Another tour de force by the Victora lab. A must read for germinal center aficionados. There goes the weekend!

YouTube video by Amanpour and Company Breakthrough Prize-Winning Biochemist on the Deadly Cost of Funding Cuts | Amanpour and Company

David Liu @harvard.edu beautifully articulates the criticality of basic science funding for developing revolutionary therapeutics like life-saving base editors 👏

youtu.be/8YhJM6zxYDw?...

AKT signaling restrains tumor suppressive functions of FOXO transcription factors and GSK3 kinase in multiple myeloma Key Points. FOXO transcription factors and the GSK3 kinase are pivotal tumor suppressors restrained by AKT activity in MM cells.FOXO and GSK3 destabilize M

This aligns with findings from our lab where we show that AKT inhibition synergizes with MCL-1 inhibition to induce cell death in myeloma cells. ashpublications.org/bloodadvance...

Exploring BCL2 regulation and upstream signaling transduction in venetoclax resistance in multiple myeloma: potential avenues for therapeutic intervention - Blood Cancer Journal Blood Cancer Journal - Exploring BCL2 regulation and upstream signaling transduction in venetoclax resistance in multiple myeloma: potential avenues for therapeutic intervention

Interesting study on how to sensitize myeloma cells to the BCL2 inhibitor venetoclax by interfering with signal transduction pathways. #myeloma #science 🩸🔬https://www.nature.com/articles/s41408-025-01215-x

This is what we know about the so-called 'epithelial-mesenchymal transition'

'Lack of basic rationale in epithelial-mesenchymal transition and its related concepts'
cellandbioscience.biomedcentral.com/articles/10....

"WE'VE ARRANGED A society based on science and technology, in which nobody understands anything about science technology. And this combustible mixture of ignorance and power, sooner or later, is going to blow up in our faces. Who is running the science and technology in a democracy if the people don't know anything about it?" "Science is more than a body of knowledge, it's a way of thinking. A way of skeptically interrogating the universe with a fine understanding of human fallibility. If we are not able to ask skeptical questions, to interrogate those who tell us that something is true, to be skeptical of those in authority, then we're up for grabs for the next charlatan, political or religious, who comes ambling along."

I think a lot about what Carl Sagan said in one of his final interviews.

And, again, WHERE IS #BIGPHARMA in defending #basicscience? laying low? playing dead? Waiting it out? Do SOMETHING! SPEAK UP! Use your gigantic lobbying machine to defend us instead of peddling your wares and increasing your profits. Or do you think highly trained workforce grows on trees?

Antibodies don't work.

NLRP3 is by far the most studied inflammasome — yet <30% of commercial antibodies were specific.

Only 4 of 14 tested antibodies detected NLRP3 specifically.

Antibodies must be validated before use.

Full report by @ycharos.bsky.social : zenodo.org/records/1162...

Microbial metabolite drives ageing-related clonal haematopoiesis via ALPK1 - Nature ADP-heptose binds to ALPK1, triggering transcriptional reprogramming and NF-κB activation, endowing pre-leukaemic cells with a competitive advantage due to excessive clonal proliferation.

B͓̊å͓c͓̊t͓̊e͓̊r͓̊i͓̊å͓l͓̊ s͓̊ů͓g͓̊å͓r͓̊ f͓̊ů͓e͓̊l͓̊s͓̊
c͓̊å͓n͓̊c͓̊e͓̊r͓̊ r͓̊i͓̊s͓̊k͓̊

Study in 𝘕𝘢𝘵𝘶𝘳𝘦 finds ADP-HEPTOSE, a bacterial sugar produced by Gram- gut flora, leaks into the bloodstream with age, activating NF-κB, giving pre-leukaemic blood cells a growth edge, and triggering dangerous clonal haematopoiesis

Starczynowski Lab U Cincinnati

Comprehensive interrogation of synthetic lethality in the DNA damage response Nature - Combinatorial CRISPRi screening was used to map genetic interactions in DNA damage response pathways, revealing known and new connections, including the roles of WDR48 and USP1 in...

Thrilled to see this “veritable tour de force” led by John_C_Fielden from Jacob Corn lab out @nature.com, rdcu.be/ehd4E. This @erc.europa.eu funded project uses #CRISPRi to systematically scan 548 DDR genes for synthetic lethal interactions, ~150,000 pairwise combinations!

our work on the molecular differences between transcription factor isoforms is out now in Molecular Cell!

key point: 2/3rds of TF isos differ in properties like DNA binding & transcriptional activity

many are "negative regulators" & misexpressed in cancer

www.sciencedirect.com/science/arti...

French scientist denied US entry after phone messages critical of Trump found France’s research minister said the scientist was traveling to Houston for a conference when his phone was searched

Freedom of speech? Don't travel to the US, it is not save

French scientist denied US entry after phone messages critical of Trump found

France’s research minister said the scientist was traveling to Houston for a conference when his phone was searched

www.theguardian.com/...
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This is beyond stupid, already extensively debunked and based on a fraudulent study. What would yet another study do when they are not interested in facts to begin with??

Great people, awesome science. Highly recommend!

PVV leader Wilders stands behind Ukraine 'with conviction' Dutch leader Geert Wilders supports Zelensky amidst US-Ukraine clash; calls anti-Trump sentiment unproductive.

How a small country can even be smaller: PVV MPs applauding the attack of Zelensky by Trump and Vance. This bunch is not to be trusted, their conviction lies with Russia. Let’s call them what they are: TRAITORS. Please pull the plug on this coalition. www.brusselstimes.com/1467549/pvv-...

Deep profiling of B cells responding to various pathogens uncovers compartments in IgG memory B cell and antibody-secreting lineages Deep profiling of B cells responding to various pathogens uncovers immune memory B cells and plasmablast lineages.

Deep profiling of B cells responding to various pathogens uncovers immune memory B cells and plasmablast lineages
www.science.org/doi/10.1126/...

Thanks for compiling this list and including me Jonathan! 👍🏻🙏

go.bsky.app/BtBs6xj Still slowly building a myeloma research oriented starter pack, let me know if you are missing.

4-year PhD studentship available in my lab to study helper helicase function in eukaryotic DNA replication. Happy to receive any enquiries directly to me. Come join us and add your figure to the lab lego collection!

institute-genetics-cancer.ed.ac.uk/igc-graduate...

Exciting times in the lab! Kicking off a genome-wide CRISPR-Cas9 screen in myeloma cells. Shoutout to @guusdewilde.bsky.social and (no-BlueSky) Maaike Janssens for their invaluable contribution to this project. Let’s unravel some myeloma mysteries! 🩸🔬 #cancerresearch #CRISPR #myeloma

Daratumumab plus bortezomib, lenalidomide and dexamethasone for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: the randomized phase 3 CEPHEUS study - Nature Medicine In the phase 3 CEPHEUS trial, patients with transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma were treated with subcutaneous daratumumab plus bortezomib, lenalidomide and d...

Quadruplets induction regimens are the established standards of care now in newly diagnosed MM, just out 🎉👇🏽
#MyelomaSky

@mskcancercenter.bsky.social
@imfmyeloma.bsky.social
@themmrf.bsky.social
@healthtreeorg.bsky.social

www.nature.com/articles/s41...