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.

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.

🙏 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.

🔬 2/ We systematically analyzed how chromocenter structure, HP1α binding, histone marks and transcription respond to the recruitment of transcriptional activators with different strengths (VP16, p65, VPR).