Bart Deplancke

This preprint closes a long development phase…
but opens a new frontier: morphology as a quantitative, molecularly anchored measurement modality.
If this resonates with your work, we’d love to connect.
Thanks again to the entire team and looking forward to exciting new IRIS adventures 🚀!

IRIS also revealed that subtle nuclear morphologies correspond to distinct molecular states, including the previously puzzling T cell stripy nuclear phenotype (collab. w/ @BerendSnijder's lab; Hale et al., Science, 2024), now shown to map to a specific transcriptomic program.

We also show that IRIS enables prediction of transcriptomes directly from images (#ML). Models trained on IRIS data recover gene-level variation, cell-cycle phase, and cell identity from morphology alone.

We uncovered phase-specific TF activity, revealing how DREAM complex repression, FUCCI intensity, and cell-cycle speed are linked. IRIS detects quiescence-primed vs fully quiescent states & shows that slowly cycling cells display stronger DREAM-mediated repression, insights missed by RNA-only tools.

As a 1st application, we used IRIS to profile >5k FUCCI-3T3 cells, reconstructing the full continuous #cell-cycle from morphology + RNA; identifying 670 cycling genes. IRIS’s morphology-anchored cell-cycle angle aligns with Seurat/Tricycle but provides smoother, higher-resolution structure.

IRIS solves a long-standing gap: #imaging and droplet-based sequencing were never truly connected at single-cell resolution. Here, every cell is imaged first (BF + 4 fluorescent channels) → then deterministically barcoded → then sequenced, enabling single cell #phenomics.

Overview of Integrated Robotic Imaging and Sequencing, IRIS

We just released IRIS (7+yrs project), a tech we believe will transform cell biology by pairing high-resolution cell images with matched #scRNAseq, letting us interpret cellular form by its molecular ground truth.
Huge tx to @JohannesBues, @JoernPezoldt, @CamilleLambert et al.
shorturl.at/zgY8Z

(1/13) Excited to share the outcome of the IBIS Challenge! The IBIS challenge united dozens of teams across the world in tackling the problem of modeling transcription factor (TF) binding specificity using a diverse collection of experimental datasets for understudied human TFs.

🧵2/ Across 384 TFs and ~40,000 cells, we found:
– Nonlinear, dose-sensitive reprogramming responses
– TFs triggering different fates at low vs high dose
– Same dose, different outcome = hidden complexity
– TF pairs flipping between synergy & antagonism based on dose ratio

Dissecting the impact of transcription factor dose on cell reprogramming heterogeneity using scTF-seq - Nature Genetics This study introduces single-cell transcription factor (TF) sequencing, a single-cell barcoded and doxycycline-inducible TF overexpression approach that reveals dose-sensitive functional classes of TFs and cellular heterogeneity by mapping TF dose-dependent transcriptomic changes during the reprogramming of mouse embryonic multipotent stromal cells.

🧵1/ Excited to share our new paper introducing a new #singlecell assay: scTF-seq, a high-throughput single-cell approach to explore how transcription factor (TF) dose shapes cell identity and reprogramming outcomes. 🔗 www.nature.com/articles/s41... Big congrats to the entire team @EPFL & @SIAT_China

Faculty Position in Life Science Engineering The School of Life Sciences at EPFL invites applications for a faculty position in life science engineering. Appointments will be at Tenure Track Assistant Professor or at Associate Professor level. W...

Outstanding Faculty opportunity in the broad area of 'life sciences engineering' @EPFL School of Life Sciences, open to both junior and senior researchers. We may prefer metabolism-centric applications but remain open to outstanding applications across domains:
www.epfl.ch/about/workin...

Fantastic work by Camille Lambert, Guido van Mierlo, Orane Guillaume-Gentil and Johannes Bues. For a related review on 'The evolution of DNA sequencing with microfluidics', pls also see: www.nature.com/articles/s41...

Engineering next-generation microfluidic technologies for single-cell phenomics - Nature Genetics Research is moving from a gene- and protein-centric view toward a holistic understanding of cellular phenotypes. This Review discusses the technological microfluidics challenges that must be addressed...

Our new review on how #microfluidics has been key for (#single-cell) #genomics & how it will remain essential to support this new era of single cell #phenomics: www.nature.com/articles/s41.... Great timing for the Microfluidics Gordon Research Conference here in Lucca! www.grc.org/physics-and-...

Design principles of cell-state-specific enhancers in hematopoiesis Screen 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...

🚀 study: www.cell.com/cell/fulltex... from @larsplus.bsky.social et al: via enhancer design from scratch, 3 principles emerged: 1) TF binding strength = activation 'or' repression; 2) Same motif ≠ same output in all cell states; 3) 2 activators ≠ activation - combos can repress! #geneRegulation

Impressive, new snRNA-seq atlas across 8 mouse strains & tissues reveals how genetics shapes cell-type-specific gene expression. A key resource for decoding trait variation, disease mechanisms & guiding mouse model design. #Genomics #SingleCell #PrecisionMedicine. www.biorxiv.org/content/10.1...

Spatial multi-omics reveals cell-type-specific nuclear compartments - Nature A genomic barcoding scheme called two-layer DNA seqFISH+ enables the simultaneous mapping of more than 100,000 loci and has been used to identify cell-type-specific subnuclear compartments in the mous...

Amazing 🚀 study w/ DNA seqFISH+, enabling mapping of 100,049 genomic loci, together with the nascent transcriptome for 17,856 genes, yielding unpredented insights into subnuclear structures in single cells www.nature.com/articles/s41...

Great opportunity! 🎆

CREsted: modeling genomic and synthetic cell type-specific enhancers across tissues and species Sequence-based deep learning models have become the state of the art for the analysis of the genomic regulatory code. Particularly for transcriptional enhancers, deep learning models excel at decipher...

New tool 💪 from @steinaerts.bsky.social lab: CREsted, a DL-based approach for predicting cell type-specific reg. elements, applying it to many datasets, incl. mouse cortex, human PBMCs & glioblastoma, demonstrating its ability to identify key TF binding sites: www.biorxiv.org/content/10.1...

Science under attack: a growing list of statements from journals
@jama.com
jamanetwork.com/journals/jam...

@plos.org
theplosblog.plos.org/2025/02/plos...

@science.org
www.science.org/doi/10.1126/...

@nature.com
www.nature.com/articles/d41...

@embopress.org
www.embopress.org/doi/full/10....

Sounds very exciting, very much looking forward!

Tahoe-100M: A Giga-Scale Single-Cell Perturbation Atlas for Context-Dependent Gene Function and Cellular Modeling Building predictive models of the cell requires systematically mapping how perturbations reshape each cell’s state, function, and behavior. Here, we present Tahoe-100M , a giga-scale single-cell atlas...

#scRNAseq to the next level: www.biorxiv.org/content/bior.... Mindbogglingly 100M cell large dataset involving 50 cancer cell lines and 1,100 molecule perturbations 🤩 — an absolute feast for the data-hungry ML/AI field, poised to advance cell understanding and modeling.

Really cool method 'Trace-n-seq' that allows for the molecular characterization of single neurons that innervate the pancreas and how this is altered in a cancer context at high resolution. www.nature.com/articles/s41...

wow 🚀! Need to look into the details, but sounds really exciting: Seq-Scope-X --> new spatial transcriptomics & proteomics technology that achieves sub-200 nm super-resolution, surpassing the diffraction limit of optical microscopy by physically enlarging tissues. www.biorxiv.org/content/bior...

👍

Bart Deplancke ‪Professor in Systems Biology and Genetics at EPFL‬ - ‪‪Cited by 18,422‬‬ - ‪genetics‬ - ‪transcription‬ - ‪systems biology‬ - ‪single cell‬

Happy to be part of the feed Erik, thanks for the initiative. scholar.google.ch/citations?us...

A new mechanism for cancer-induced immune evasion. We knew about cancer cells hijacking mitochondria. Now we learn about how their mitochondrial transfer to T cells impairs the tumor immune response.
www.nature.com/articles/s41...
www.nature.com/articles/d41...

Interesting study showing how a heart disease-linked TF, TBX5, regulates 3D chromatin independently of transcription, via structural and cohesin-regulating roles in a dose-dependent fashion www.biorxiv.org/content/10.1...

Not that I know of, but it is for sure a good idea. Someone simply needs to start it! 💪

Transcript-specific enrichment enables profiling of rare cell states via single-cell RNA sequencing - Nature Genetics Programmable Enrichment via RNA FlowFISH by sequencing (PERFF-seq) isolates rare cells based on RNA marker transcripts for single-cell RNA sequencing profiling of complex tissues, with applicability t...

Cool new method (PERFF-seq) for profiling rare cell states via #scRNAseq, allowing for the isolation of rare cell populations by fluorescently labeling specific transcripts after which the respective cells are sorted, thus uncovering more phenotypic heterogeneity. www.nature.com/articles/s41...

Fully agree with Carlos! Having peers at a similar career stage has been invaluable—building lasting relationships, inspiring great science, and acting as soundboards for new ideas. These connections still help navigate the daily grind of being a PI. So excited to see the JEDI Phoenix rise again! 🚀✨