bioRxiv (Cold Spring Harbor Laboratory)

Cannabis sativa is a dioecious crop whose male plants carry a Y chromosome entirely excluded from every genome-wide association study (GWAS) published to date, despite its direct relevance to agronomic trait variation. Here, we present the first sex chromosome-aware GWAS of cannabis, integrating both ChrX and ChrY across 145 landrace accessions and 27 agronomic traits. By combining SNP-based GWAS…

Protein biogenesis is a stress- and error-sensitive process that can lead to nascent protein misfolding and aggregation, challenging cellular proteostasis. Co-translational ubiquitination (CTU) is a critical surveillance mechanism, yet its regulatory principles remain unclear due to limited known substrates and the lack of translatome-wide methods to query CTU. Here, we introduce UbSeRP, an appro…

Species' complex demographic history, including population size changes, isolation and gene flow, shapes patterns of genetic variation and deleterious load. In small and declining populations, understanding these processes is critical for predicting inbreeding depression and extinction risk. The Rice's whale (Balaenoptera ricei) is a newly described baleen whale species resident to the heavily in…

Head and neck squamous cell carcinoma (HNSCC) remain a major clinical challenge due to its high heterogeneity and limited therapeutic response, resulting in a 5-year overall survival rate of only ~50%. Identifying molecular pathways that drive tumor progression while suppressing anti-tumor immunity is therefore critical for developing more effective therapies. NAT10 (N-acetyltransferase 10) is th…

Efficient and heritable genome editing in plants remains constrained by transformation bottlenecks and reliance on tissue culture-based regeneration. Targeting the male germline offers a promising alternative for DNA-free genome modification. Here, we report a polymeric nanoparticle platform for the delivery of RNA-based CRISPR/Cas9 components into Arabidopsis thaliana pollen, establishing a foun…

Flexible decision making depends on retrieving and recombining memories. Yet because this process unfolds covertly, its governing principles remain unknown. Here we use gaze reinstatement to uncover the hidden dynamics and computational logic of memory retrieval during flexible behavior. As people deliberated on a blank screen, they directed their gaze toward the encoding locations of decision-re…

Bread wheat (Triticum aestivum L.) possesses a large and highly repetitive allohexaploid genome and annotation requires extensive protein-level validation. We developed a genome-based wheat proteogenomics workflow integrating large-scale MS/MS reanalysis, GFF3-based peptide coordinate reconstruction, thorough validation, and genome browser-compatible peptide deployment against the IWGSC RefSeq v2…

The histone variant H2A.J is implicated in radiation-induced senescence by promoting the transcription of inflammatory genes. While H2A.J expression increases in renal tubular epithelial cells (TECs) following ionizing radiation (IR), its functional role remains poorly understood. To investigate this, constitutive H2A.J knock-out (KO) mice and wild-type (WT) controls were subjected to CT-guided I…

Volatile organic compounds (VOCs) mediate plant–plant signalling and may contribute to phenotypic differentiation among populations. However, the extent to which VOC-mediated signalling varies among locally adapted populations, and how VOC traits relate to major fitness-related traits, remain poorly understood. We conducted a greenhouse experiment using two genetically and phenologically divergen…

The tumour suppressor LKB1 (STK11) is implicated in diverse cancers, yet its transcriptomic role in breast cancer remains poorly defined. Here, we integrate bulk-tumour genomic analysis of the METABRIC cohort, CRISPR-Cas9-mediated STK11 knockout in human breast cancer cell lines, single-cell RNA sequencing of patient tumours, and a novel Lkb1 murine model to characterise LKB1-dependent transcript…

Age-related macular degeneration (AMD) is a leading cause of central vision loss. Immunofluorescence and gene expression studies in human donor eyes have shown that choriocapillaris endothelial cells (CECs) are lost before retinal pigment epithelium (RPE) degeneration, leaving extracellular matrix–filled empty lumens known as ghost vessels. To investigate disease mechanisms, we generated CECs fro…

One-carbon (1C) metabolism is frequently upregulated in cancer to support anabolic growth and nucleotide biosynthesis. However, the contribution of mitochondrial 1C metabolism to cancer stemness and metastatic progression remains incompletely understood. Here, we identify methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L), a mitochondrial 1C metabolic enzyme, as a critical regulator of brea…

Organotypic brain slice cultures (OSCs) provide a physiologically relevant model for recapitulating complex tissues in vitro. However, the longitudinal monitoring of dynamic processes in OSCs through high-resolution imaging is limited in standard culturing methods, as they rely on slice placement on porous membranes at the air-liquid interface to preserve tissue viability. Here, a new experimenta…

Multiple myeloma (MM) is a heterogenous cancer that remains mostly incurable. A unifying feature of MM cells is a highly interconnected network of transcription factors and co-factors that coordinate the activity of super-enhancers to enforce myeloma cell identity. Targeting this network offers a promising avenue for therapeutic intervention across genetically diverse myeloma sub-types. Using int…

The Ki-67 protein is a widely used marker of mammalian cell proliferation that plays critical roles in heterochromatin organisation and mitotic perichromosomal layer formation. Thus, its apparent restriction to vertebrates is puzzling. However, sequences with limited homology to subdomains of Ki-67 are present in genomes from some non-vertebrate species. Here, using structural modelling, biophysi…

Hematopoietic stem and progenitor cells (HSPCs) reside in a mechanically distinct bone marrow niche, yet how niche biomechanics shape genome stability and stress responses has been difficult to test because conventional two-dimensional (2D) culture lacks marrow viscoelasticity and uses surfaces that activate platelets, confounding hematopoietic readouts. Here, we show that this methodological gap…

Fibroblast transcriptomic states reflect physiological and pathological tissue contexts, yet the upstream determinants that stabilize these states remain poorly defined. Integrins mediate extracellular matrix (ECM) adhesion and biochemical signaling, but whether they encode mechanical constraints into stable transcriptomic programs is unclear. Using engineered mouse fibroblasts, bulk and single-c…

Excitation/inhibition (E:I) imbalance is a convergent mechanism in neurodevelopmental disorders (NDDs), yet whether NDD risk genes disrupt excitatory and inhibitory neurons through shared or distinct molecular programs remains poorly understood. Using human pluripotent stem cell-derived cortical projection and medial ganglionic eminence-like inhibitory neurons, we show that loss-of-function mutat…

Variation in APOE, notably the ϵ4 allele, profoundly shapes risk and severity of late-onset Alzheimer's disease (AD), yet how it remodels human microglial states remains unresolved. We combine spatially resolved proteomic profiling with single-nuclear multiomic analyses to define microglial organization across APOE3/3 and APOE4/4 genotypes in AD. Quantifying condition-associated variation across …

The ventromedial prefrontal cortex (VMPFC) has been repeatedly implicated in affect, valuation, and social cognition, yet how these diverse functions are organized within a single cortical territory has remained unresolved. Here, we integrate large-scale meta-analysis, individual-level task fMRI, artificial neural-network encoding models, and multimodal connectivity analyses to reveal the interna…