Karsten Rippe

8/ 🤘 For those about to rock (around the Christmas tree), we salute you 🎸🎄: Isabelle Seufert & our team from @dkfz.bsky.social & BioQuant & @akispapantonis.bsky.social, Philipp Mallm, @s-anders.bsky.social & Petros Kolovos labs with support from @spp2202.bsky.social & @mspacealliance.bsky.social.

7/ 🌟 The broad applicability of our RWireX framework was shown in different cellular systems. In human blood cells, cell-type-specific regulatory programs could be distinguished, e.g., the DCs at the CD22 and the TBX21 loci had highest activity in B cells and mature CD8+ T cells, respectively.

6/ 🎯 Our AC/DC framework reveals how cells achieve precise gene control. TRGs with TF promoter binding show fastest induction. DCs enable coordinated burst-size increases, while ACs allow fine-tuned gene-specific regulation—working together to support complex programs.

5/ ⛰️ DCs are larger contiguous regions of simultaneously accessible chromatin sites. These domains exhibit locally increased transcription factor binding activity and may represent the genomic footprints of TF hubs.

4/ 🔗 ACs denote interactions between separated regulatory sites at ATAC peaks. We observed differences between rare and frequently occurring ACs, suggesting distinct roles of stochastic vs. architectural links.

3/ 💻 Using our new RWireX software (github.com/RippeLab/RWi...), we distinguish two regulatory chromatin modules: ACs (autonomous links of co-accessibility between separated sites of 1 kb size) and DCs (domains of contiguous co-accessibility of ~200 kb) that both can co-exist.

2/ 🔍 We investigated the proinflammatory response to TNF in primary human cells using #scRNA and #scATAC sequencing and fluorescence microscopy. We identified ~1,500 TNF-regulated genes (TRGs) that often clustered in the genome and exhibited induced co-expression.

1/ 🎄 We got our Christmas present today: "Two distinct chromatin modules regulate proinflammatory gene expression" is now published @natcellbio.nature.com doi.org/10.1038/s415.... Our study introduces a scATAC-seq-based framework for genome-wide analysis of gene regulation features.

Happy to report that the Xenium system for spatial transcriptomics in the Single Cell Open Lab www.dkfz.de/en/single-ce... @dkfz.bsky.social was the first one worldwide to pass the mark of 100 runs according to @10xgenomics.bsky.social. And it keeps on running with another one, so stay tuned...

"In our view, it [hexanediol] should thus be avoided and not be used as evidence for the formation of an assembly via phase separation or the fluid-like nature of a condensate in vitro or in vivo." doi.org/10.1038/s414...

These features allow it to predict immunotherapy response and point to potential universal T cell based therapies. Great multi-group effort led by Mirco Friedrich together with @michael-platten.bsky.social, @raabms.bsky.social, @stefaneichmueller.bsky.social, and many more collaborators.

Glad that the preprint on identifying and characterizing rare tumor-reactive T cells in multiple myeloma & AML patients is out now doi.org/10.1101/2025.... Single-cell TCR and transcriptome profiling & immunopeptidomics revealed conserved programs and shared non-canonical antigens.

Liquid-liquid phase separation of HP1? Not in our mouse fibroblasts… This paper by the Fabian Erdel group offers a fresh perspective on how this can be reconciled with seemingly conflicting reports: The phase separation propensity of HP1 decreases from yeast → fly → mouse. doi.org/10.1038/s414...

3/ Great joint effort with Philipp Mallm and the Single Cell Open Lab @dkfz.bsky.social, led by Anne Rademacher, Alik Huseynov, and Michele Bortolomeazzi, with key contributions from our colleagues at KiTZ Heidelberg, supported by the @mspacealliance.bsky.social program of @hlsalliance.bsky.social.

2/ Using medulloblastoma cryosections, we analyzed sensitivity, specificity, and spatial signal patterns to distinguish background from rare-cell signals. We also show how reimaging slides improves cell segmentation—and enables additional transcript and protein readouts from the same section.

Comparison of spatial transcriptomics technologies using tumor cryosections - Genome Biology Background Spatial transcriptomics technologies are revolutionizing our understanding of intra-tumor heterogeneity and the tumor microenvironment by revealing single-cell molecular profiles within the...

1/ Spatial transcriptomics technologies are rapidly evolving. We compared five methods—Visium, RNAscope HiPlex, Molecular Cartography, Merscope, and Xenium—and developed technology-agnostic quality control metrics to guide their use: doi.org/10.1186/s130...

How do transcription compartments form — and does phase separation drive gene expression? I enjoyed discussing these questions with @akispapantonis.bsky.social a lot, and we put our thoughts together for @naturerevgenet.bsky.social, now out at rdcu.be/erP1u

From enhancer hijacking to ecDNA and onco-condensates – we review how changes in nuclear architecture drive oncogenic gene expression by disrupting enhancer–promoter communication. doi.org/10.1002/ijc..... Kudos to Isabelle Seufert, @claire-vrgs.bsky.social and Sina Wille 👏

Thanks to the Wissenschaftsrat @wissrat.bsky.social — the German Science and Humanities Council — for their clear statement expressing solidarity with US research institutions and scientists and defending academic freedom. www.wissenschaftsrat.de/SharedDocs/P...

Trump Administration Has Begun a War on Science, Researchers Say (Gift Article) Nearly 2,000 scientists urged that Congress restore funding to federal agencies decimated by recent cuts.

“We all rely on science.” U.S. scientists are speaking out for scientific integrity and academic freedom. What they’re doing matters. We owe them our solidarity and a clear stand beside them.
www.nytimes.com/2025/03/31/s...

A mechanism for maintaining and spreading H3K9me3 in heterochromatin from the Fejes Toth and Aravin labs that depends on the local H3K9me3 density: HP1 dimers recruit SetDB1 to chromatin by simultaneously binding H3K9me3 on histone H3 and auto-methylated SetDB1. www.biorxiv.org/content/10.1...

Fakten sind das Rückgrat unserer Demokratie - Online-Petition Liebe Mitbürgerinnen und Mitbürger, als Wissenschaftlerinnen und Wissenschaftler arbeiten wir täglich daran, die Grundlagen für fundierte Entscheidungen und Innovationen zu schaffen – basierend auf üb...

Fakten sind das Rückgrat unserer Demokratie
Facts are the backbone of our democracy
When facts are treated as opinions and replaced by rhetoric or propaganda, meaningful discourse suffers, threatening democracy and leaving it vulnerable to manipulation.
www.openpetition.de/!ychtb

www.uni-heidelberg.de/en/newsroom/...

🙏 9/ Kudos to lead author Robin Weinmann, @udupaarjun.bsky.social and @janfabio.bsky.social for shaking up heterochromatin and cracking this puzzle! Thanks to @dfgpublic.bsky.social for funding us in the SPP2191 program.

💡 8/ Time to think different: HP1α isn't a global chromatin compaction machine, but a local transcriptional gatekeeper that strong activators can bypass. A new view on how heterochromatin does its job.

💻 7/ Our mathematical modeling showed it could be beautifully simple: Each repeat unit independently switches between silent/active states. No fancy mechanisms needed - basic ligand binding math explains everything we see, with no evidence for HP1α phase separation in our mouse fibroblasts.

🔍 6/ Looking up close with super-resolution microscopy revealed: HP1α sits in small ~50 nm clusters that persist during activation. Just good old chromatin binding at work, with additional HP1α molecules recruited through protein-protein interactions.

💭 5/ Another surprise: Chromatin can unpack without histone acetylation! In cells lacking HP1α/H3K9me3, VP16 can decondense chromatin and activate genes without enriching H3K27ac - revealing an alternative paths to open up chromatin.

🚫 4/ HP1α acts as a local transcriptional brake in two ways: complete silencing or partial attenuation of transcription. Weak activators like VP16 are blocked, while strong ones like VPR can overcome this barrier - shown both at chromocenters and using a reporter system.

💥 3/ The big surprise: Even when the strongest activator VPR decondenses chromatin and drives transcription, HP1α and H3K9me3 stay put! This challenges the dogma that these repressive chromatin features must be removed for gene activation.