Schwager, A. | bioRxiv Science

bioRxiv2026

Translocation-driven chr19-der(14) interaction is associated with disease-specific transcriptional programs in mantle cell lymphoma

Mantle cell lymphoma (MCL) is defined by the t(11;14)(q13;q32) translocation, which drives constitutive CCND1 expression, yet the broader regulatory consequences of this rearrangement remain incompletely understood. Here, we combined transcriptomic, epigenomic, Hi-C, and 3D-FISH analyses in primary MCL samples and cell lines to investigate the genome-wide impact of t(11;14) on chromatin organization and gene regulation beyond the rearranged chromosomes. We show that MCL cells exhibit widespread enhancer activation, accompanied by expansion of super-enhancer regions. The translocated CCND1 locus repositions toward the nuclear interior and acquires enhancer-like features. Genome-wide analysis highlighted chromosome 19 as a hotspot of transcriptional upregulation. Notably, Hi-C and 3D-FISH revealed recurrent interchromosomal contacts between chromosome 19 and the CCND1 locus, preferentially involving the derivative chromosome. These contacts colocalize with active RNA polymerase II and are associated with increased expression of nearby chr19 genes, suggesting an association between spatial proximity and transcriptional activation in trans. Minnelide treatment reduced chromatin accessibility at the CCND1 locus, decreased the frequency of chr19-der14 interactions, and partially reversed the MCL transcriptional program, while exerting strong anti-tumor effects in vitro and in vivo. Together, these findings identify a recurrent interchromosomal interaction associated with coordinated gene activation in MCL and suggest that spatial genome reorganization contributes to disease-specific transcriptional programs.

cancer biology↗

bioRxiv2026

Matched single-cell chromatin, transcriptome, and surface marker profiling captures in vivo epigenomic reprogramming during basal-to-luminal transition in the mammary gland

Single-cell multi-omics methods enable simultaneous mapping of chromatin states and transcriptomes, offering deep insights into gene regulation. Yet, the full potential of these approaches remains untapped for rare cell populations, as most methods require thousands of cells and are limited in their ability to capture multiple molecular layers comprehensively within the same cell. Here, we introduce OneCell CUT&Tag a user-friendly method that provides matched high-resolution epigenome, full-transcriptome, and surface marker quantification from every cell, with input as low as one cell. Using this approach, we uncovered epigenomic priming of basal cells in the mammary gland and captured the dynamics of basal-to-luminal transdifferentiation. We identified a transitional cell population with intermediate epigenomic profiles--absent in reference populations--and demonstrated a continuous epigenomic progression from basal to luminal states, while transcriptomes exhibited a binary switch. Adaptable to diverse samples and tissues, this method also revealed the role of H3K27me3 in shaping zygotic expression programs. By matching multiple layers of molecular information at single-cell resolution, OneCell CUT&Tag dissects the complementary roles of each omics layer in shaping cellular identity and function, opening new avenues to study rare and complex biological systems.

genomics↗