Karsten Rippe

HP1α binding creates a local barrier against transcription activation and persists during chromatin decondensation

Robin Weinmann, Arjun Udupa, Jan Fabio Nickels, Tsz Ching Chloe Tang et autres

Mouse pericentric heterochromatin forms compacted, transcriptionally silent domains, termed chromocenters, that are enriched in heterochromatin protein 1 (HP1). Whether HP1α represses chromocenters by binding locally or by maintaining a phase-separated compartment is unresolved. We investigated this question by recruiting transcriptional activators to …

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PA-276 Latent Effector T Cells Mediate Immunotherapy Responses in the Bone Marrow Microenvironment

Niklas Kehl, Tim R. Wagner, Simon Steiger, Tamara Boschert et autres

Latent effector T cells mediate immunotherapy responses in the bone marrow microenvironment

Niklas Kehl, Tim R. Wagner, Simon Steiger, Tamara Boschert et autres

T cell-mediated immune surveillance is critical for cancer control, yet its role in bone marrow malignancies remains poorly understood. Here, we integrate TCR profiling, HLA immunopeptidomics, and functional screening to characterize tumor-reactive T cells in the bone marrow of patients with multiple …

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HetChrom_activation: image analysis code

Robin Weinmann, Arjun Udupa, Jan Fabio Nickels, Tsz Ching Chloe Tang et autres

Image analysis code for chromocenter perturbation experiments in mouse fibroblasts and for transcription reporter array experiments in U2OS cells, as used in Weinmann et al., Molecular Cell.

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HetChrom_activation: image analysis code

Robin Weinmann, Arjun Udupa, Jan Fabio Nickels, Tsz Ching Chloe Tang et autres

Image analysis code for chromocenter perturbation experiments in mouse fibroblasts and for transcription reporter array experiments in U2OS cells, as used in Weinmann et al., Molecular Cell.

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Single-stranded telomeric repeats segregate into spatial compartments within ALT-associated PML bodies

Karsten Rippe, Emma S. Koeleman

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Multiomic profiling links L1 retrotransposition to genomic instability and ecDNA in bladder cancer

Sophia J. Pribus, Ivana Osredek, Jan Otoničar, Milena Simovic-Lorenz et autres

Bladder cancer is frequent and highly recurrent. Despite recent advances, knowledge gaps remain in molecular mechanisms underlying disease progression. In this study, we apply integrated multi-omic analyses to a cohort of 48 bladder cancer patients to comprehensively profile genetic, epigenetic, transcriptomic, and …

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ID #732 Aberrant Developmental Cell-State Programs Drives Heterogeneity in Group 3/4 Medulloblastoma

Patricia Benites Goncalves da Silva, Piyush Joshi, Konstantin Okonechnikov, Tamina Stelzer et autres

Abstract Group 3 and Group 4 medulloblastomas (MB) are among the most common and highly fatal pediatric brain cancers, characterized by marked cellular heterogeneity. Limited understanding of the molecular mechanism underlying this heterogeneity presents a profound therapeutic challenge. To understand how the …

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Mutant IDH1 blocks neutropoiesis by repressing myeloid progenitor programs

Mariam Hakobyan, Jens Langstein, Maria Jose Ramos Medina, Emely Kleinert et autres

ABSTRACT: IDH1 and IDH2 are frequently mutated in various cancers, including acute leukemias. However, the distinct mechanisms by which mutant IDH1 or IDH2 drive hematopoietic neoplasms remain poorly understood. Here, we analyzed DNA methylation in IDH1- and IDH2-mutant acute myeloid leukemia and …

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Mapping the genomic and transcriptomic features associated with telomere maintenance mechanisms in complex karyotype sarcomas

Nicola Biondi, Maria Luisa Ratto, Rajesh Pal, Tobias Rausch et autres

Abstract Complex karyotype sarcomas (CKS) are heterogeneous mesenchymal malignancies that typically lack recurrent actionable oncogenic drivers and remain therapeutically challenging. Loss of ATRX is a recurrent feature of CKS and defines a particularly high-risk subgroup. ATRX loss is also associated with activation …

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Disagreement between demultiplexing methods reveals structured cell quality gradients in multiplexed single-cell data

Ezgi Sen, Simon Steiger, Mislav Bašić, Nina Prokoph et autres

Abstract Background Single-cell multi-omics profiling of hematopoietic malignancies frequently involves pooling of patient samples before library preparation to reduce costs. Demultiplexing and quality control of the resulting sequencing data depend on experimental design, sequencing depth, and computational methods. Existing approaches benchmark individual …

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Single-stranded telomeric repeats segregate into spatial compartments within ALT-associated PML bodies

Emma S. Koeleman, Charlotte Kaplan, Maria Augusta do Rego Barros Fernandes Lima, Delia M. Braun et autres

Abstract Alternative lengthening of telomeres (ALT)-associated PML bodies (APBs) concentrate single-stranded (ss) telomeric DNA and RNA species that are critical for recombination-based telomere maintenance. However, how these species are organized inside APBs has remained invisible at microscopic resolution. Here, we map the …

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