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PubMed2026

A High-Resolution Stereo-Seq Spatial Transcriptomic Resource for Adult Holstein Cattle Liver.

The bovine liver is a highly compartmentalized organ that plays essential roles in continuous gluconeogenesis and nitrogen recycling; however, its spatial molecular architecture has remained largely uncharacterized due to the limitations of traditional bulk and single-cell approaches. To address this gap, Spatial Enhanced Resolution Omics-sequencing (Stereo-seq) was utilized to generate a subcellular-resolution (500 nm) transcriptomic map of an adult Holstein cattle liver, and a refined reference-guided workflow was implemented to overcome standard annotation limitations in livestock. Raw sequencing data were processed using the Stereo-seq Analysis Workflow and analyzed with Stereopy, Seurat, SingleR, and reference-guided workflows. Spatial aggregation was evaluated at Bin20, Bin50, Bin100, Bin150, and Bin200. Increasing bin size increased molecular identifier counts and detected-gene complexity while progressively reducing spatial granularity. Bin50, corresponding to 50 × 50 DNA nanoballs and an approximate nominal footprint of 25 × 25 µm, was therefore selected as a practical intermediate aggregation level for the primary analyses. Quality-control assessment, Leiden clustering, UMAP visualization, reference-based cell-type annotation, cluster-marker analysis, and spatial mapping of canonical hepatic genes demonstrated preservation of biologically interpretable liver transcriptional organization. Raw sequencing data processed spatial matrices, annotated objects, and analysis code are publicly available to support reanalysis and computational benchmarking. In summary, we present a Stereo-seq spatial transcriptomic resource generated from liver tissue of an adult Holstein cow. This initial resource provides a valuable foundation for future studies of bovine liver biology, comparative genomics, and the spatial basis of livestock health and production traits.

Animals↗
PubMedDate not supplied

A mouse locus at which transcription from both DNA strands produces mRNAs complementary at their 3' ends.

The organization and large size of the mammalian cell genome allows spatial separation of different transcription units. In those cases where more than one species of messenger are synthesized from the same cellular DNA sequence, they have been found to be generated from transcription proceeding in the same direction. These mRNAs always share regions of homology and can differ from one another as a result of differential processing (splicing and/or polyadenylation) or alternative initiation. In contrast, complementary mRNAs transcribed from opposite strands of the same cellular DNA sequence have not previously been observed. Here we have identified a region of mouse DNA at which processed mRNAs from two adjacent convergent transcription units overlap by 133 base pairs (bp) at their 3'-untranslated ends. One of the transcription units appears to encode a second mRNA which does not contain this overlapping region. This represents the first description of the natural occurrence of processed mammalian cell mRNAs transcribed from opposite strands of the same DNA sequence. The implications of these complementary regions in normal gene regulation are discussed in the context of the finding that the artificial introduction into cells of DNA constructs synthesizing anti-sense RNAs complementary to regions of mRNA transcribed from a chromosomal gene, can inhibit the gene's activity, presumably by the formation of double-stranded RNA.

Animals↗
PubMed2006

Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks.

We show that DNA double-strand breaks (DSBs) induce complex subcompartmentalization of genome surveillance regulators. Chromatin marked by gamma-H2AX is occupied by ataxia telangiectasia-mutated (ATM) kinase, Mdc1, and 53BP1. In contrast, repair factors (Rad51, Rad52, BRCA2, and FANCD2), ATM and Rad-3-related (ATR) cascade (ATR, ATR interacting protein, and replication protein A), and the DNA clamp (Rad17 and -9) accumulate in subchromatin microcompartments delineated by single-stranded DNA (ssDNA). BRCA1 and the Mre11-Rad50-Nbs1 complex interact with both of these compartments. Importantly, some core DSB regulators do not form cytologically discernible foci. These are further subclassified to proteins that connect DSBs with the rest of the nucleus (Chk1 and -2), that assemble at unprocessed DSBs (DNA-PK/Ku70), and that exist on chromatin as preassembled complexes but become locally modified after DNA damage (Smc1/Smc3). Finally, checkpoint effectors such as p53 and Cdc25A do not accumulate at DSBs at all. We propose that subclassification of DSB regulators according to their residence sites provides a useful framework for understanding their involvement in diverse processes of genome surveillance.

Animals↗
PubMed2005

Uniparental chromosome elimination at mitosis and interphase in wheat and pearl millet crosses involves micronucleus formation, progressive heterochromatinization, and DNA fragmentation.

Complete uniparental chromosome elimination occurs in several interspecific hybrids of plants. We studied the mechanisms underlying selective elimination of the paternal chromosomes during the development of wheat (Triticum aestivum) x pearl millet (Pennisetum glaucum) hybrid embryos. All pearl millet chromosomes were eliminated in a random sequence between 6 and 23 d after pollination. Parental genomes were spatially separated within the hybrid nucleus, and pearl millet chromatin destined for elimination occupied peripheral interphase positions. Structural reorganization of the paternal chromosomes occurred, and mitotic behavior differed between the parental chromosomes. We provide evidence for a novel chromosome elimination pathway that involves the formation of nuclear extrusions during interphase in addition to postmitotically formed micronuclei. The chromatin structure of nuclei and micronuclei is different, and heterochromatinization and DNA fragmentation of micronucleated pearl millet chromatin is the final step during haploidization.

Chromosomes, Plant↗
PubMed2026

ABCB1 Polymorphisms Influence on Temozolomide Resistance and Overall Survival in Glioblastoma Patients: A Systematic Review of Clinical Evidence.

Glioblastoma (GB), defined as IDH-wildtype CNS WHO grade 4 tumour according to the 2021 WHO classification of CNS tumours, remains a uniformly lethal malignancy in which the efficacy of temozolomide (TMZ) continues to be constrained by both intrinsic tumur biology and the pharmacological barrier imposed by the blood-brain barrier (BBB). Given the central role of the ABCB1 (MDR1/P-glycoprotein) efflux transporter in regulating CNS drug disposition, germline variation in ABCB1 has been proposed as a potential determinant of interindividual variability in TMZ response. This systematic review synthesised clinical evidence from four independent studies, encompassing more than 400 GB patients, evaluating the association between ABCB1 polymorphisms and TMZ efficacy and patients' survival. Across the available literature, the influence of ABCB1 genetic variation emerged as limited and inconsistent. An early study reported a marked survival advantage for carriers of the ABCB1 C1236T C/C genotype treated with TMZ, suggesting reduced efflux and enhanced drug exposure. However, subsequent investigations, including epigenetic analyses, high-quality multivariate survival modelling and a pharmacokinetic study demonstrating genotype-dependent differences in plasma TMZ concentrations, did not replicate a corresponding survival effect. Across the remaining cohorts, common variants such as 1236C>T, 2677G>T/A, 3435C>T and 1199G>A showed no robust association with clinical outcome, indicating that transporter-mediated modulation is likely overshadowed by dominant prognostic drivers, including MGMT methylation, IDH status and tumour heterogeneity. Collectively, current evidence does not support ABCB1 polymorphisms as reliable predictive biomarkers of TMZ response in GB. Nonetheless, the pharmacokinetic signals observed, together with emerging technologies capable of selectively modulating efflux activity at the tumour-BBB interface, point to a continued role for ABCB1 in future therapeutic strategies. Integration of transporter genomics with spatial pharmacokinetics and molecular stratification will be essential to refine drug delivery and improve outcomes in GB.

Humans↗
PubMed1981

Linkage and evolutionary diversification of developmentally regulated multigene families: tandem arrays of the 401/18 chorion gene pair in silkmoths.

The coordinately expressed silkmoth chorion genes, 401 and 18, are closely linked as a pair, in divergent orientation. Analysis of overlapping clones (chromosomal "walk") demonstrated that each of the multiple copies of this gene pair is embedded within a larger deoxyribonucleic acid unit, which is tandemly repeated in a few arrays or possibly a single array. Southern analysis and examination of clones from a single individual moth demonstrated that the repeat units are extensively polymorphic in restriction sites, length, and possibly number, no differential amplification was evident during choriogenesis. Intron and 5'-flanking sequences were shown to be specific for the 401/18 gene pair and not to be present elsewhere in the genome. The spatial distribution of variations in the genes and their flanking sequences were examined.

Animals↗
PubMed2002

Evolution of drug resistance in Candida albicans.

The widespread deployment of antimicrobial agents in medicine and agriculture is nearly always followed by the evolution of resistance to these agents in the pathogen. With the limited availability of antifungal drugs and the increasing incidence of opportunistic fungal infections, the emergence of drug resistance in fungal pathogens poses a serious public health concern. Antifungal drug resistance has been studied most extensively with the yeast Candida albicans owing to its importance as an opportunistic pathogen and its experimental tractability relative to other medically important fungal pathogens. The emergence of antifungal drug resistance is an evolutionary process that proceeds on temporal, spatial, and genomic scales. This process can be observed through epidemiological studies of patients and through population-genetic studies of pathogen populations. Population-genetic studies rely on sampling of the pathogen in patient populations, serial isolations of the pathogen from individual patients, or experimental evolution of the pathogen in nutrient media or in animal models. Predicting the evolution of drug resistance is fundamental to prolonging the efficacy of existing drugs and to strategically developing and deploying novel drugs.

Antifungal Agents↗
PubMed2026

Decoding glioblastoma evolution and heterogeneity through mechanistic modeling: implications for clinical translation.

Glioblastoma (GBM) is one of the most aggressive and lethal primary brain tumors in adults, characterized by dynamic clonal evolution and extensive genomic, cellular, spatial, and microenvironmental heterogeneity. Multi-omics studies have revealed that GBM follows complex evolutionary trajectories involving genetic, epigenetic, transcriptional, and immune-microenvironmental remodeling as tumors grow, adapt to the brain microenvironment, and acquire therapeutic resistance. Increasing evidence suggests that GBM may originate from aberrant neural stem or progenitor cells, including those residing in the subventricular zone, and that glioblastoma stem cells (GSCs) contribute to tumor propagation, heterogeneity, and recurrence. A key conceptual challenge is to reconcile hierarchical cancer stem cell models, in which GSCs are viewed as relatively stable tumor-propagating subpopulations, with dynamic state plasticity models, in which stem-like properties can be reversibly acquired or lost during transitions among proneural-like, mesenchymal-like, invasive, and therapy-tolerant states. Recent advances in single-cell profiling, spatial transcriptomics, lineage tracing, organoid culture, 3D bioprinting, genetically engineered models, and artificial intelligence (AI)-assisted computational modeling have substantially improved the ability to study these processes. However, no currently available model fully recapitulates human GBM heterogeneity, recurrence, treatment history, and tumor-microenvironment interactions. Therefore, model selection should be guided by clearly defined mechanistic questions rather than by reliance on any single platform. This review summarizes current advances in in vitro, ex vivo, in vivo, and computational models for studying GBM evolution and heterogeneity, and discusses how integrated model pipelines may improve preclinical drug testing, treatment-response prediction, and precision neuro-oncology.

Humans↗
PubMed1991

Experiments on chromosome separation and positioning in Escherichia coli.

The way in which sister genomes are spatially separated after replication and positioned in sister cells after division remains unknown for prokaryotes. Experiments with Escherichia coli suggest that individual "chromosomes" (folded, covalently closed circular DNA molecules) are fixed in position within growing cells both before and during replication, but that they are rapidly moved apart by a fixed distance (unit length) immediately after replication has been completed. Such a mitosis-like mechanism accounts for the aberrant positions of DNA and septa in cells in which the normal coordination between DNA replication and cell elongation has been perturbed.

Cell Division↗
PubMed1995

Chromosome identification and mapping in the grass Zingeria biebersteiniana (2n = 4) using fluorochromes.

The grass Zingeria biebersteiniana is one of five angiosperms known with 2n = 2x = 4. Its chromosomes were studied using fluorochrome banding and fluorescence in situ hybridization (FISH). The large pericentromeric region fluoresced much more brightly on chromosome 2 than on chromosome 1, using two different fluorochrome banding methods. These offer rapid and reliable means for identifying chromosomes and work throughout mitosis. FISH located the major site of 18S-26S rDNA sequences at the secondary constriction, which is proximal to two minor sites, all on the short arm of chromosome 1. Two 5S sites were also detected, the most distinct on the short arm of chromosome 2 and the other apparently co-localized with part of the major 18S-26S rDNA cluster on chromosome 1. These results constitute the first steps in constructing a physical gene map for Z. biebersteiniana. Such information may facilitate future studies of the organization and reorganization of grass genomes, including research into the spatial arrangement of the genome in Zingeria nuclei and much wider comparisons of synteny and genome evolution in grasses.

Centromere↗
PubMed2006

Spatial covariation of mutation and nonsynonymous substitution rates in vertebrate mitochondrial genomes.

Mitochondrial genomes encode fundamental subunits of the basic energy producing machinery of eukaryotic cells that are under strong functional constraint. Paradoxically, these genes evolve rapidly in general, and there is substantial variation in evolutionary rates among genes within genomes. In order to investigate spatial variation in selection intensity, we conducted tests of neutrality using ratios of synonymous to nonsynonymous substitutions (dN/dS = omega) on numerous protein gene segments from fishes and mammals. Values of omega were very low for nearly all genomic regions. However, values of both omega and dN varied in a clinal pattern with increasing distance from the light-strand origin of replication. Spatial heterogeneity of nonsynonymous substitution rates exhibits a significantly positive correlation with variation in mutation rates that are related to the mode of mitochondrial DNA replication. The finding that nonsynonymous substitution rates are proportional to mutation rates is expected if a majority of substitutions are selectively neutral or slightly deleterious. Spatial patterns of among-gene variation in nonsynonymous rates were highly similar between fishes and mammals, suggesting that forces governing mitochondrial gene evolution have remained relatively constant over 450 Myr of vertebrate evolution. Conservation of substitution patterns despite major shifts in thermal habit and metabolic demands among taxa implicates a conserved replication mechanism controlling relative mutation rates as a major determinant of mitochondrial protein evolution.

Animals↗
PubMed2025

Single-cell-scale spatial transcriptome of the developing and adult mouse ovary.

Mammalian ovary development is essential for female fertility, involving the complex spatial patterning of diverse cell types to establish the finite reserve of ovarian follicles. While single-cell transcriptome analyses have provided important insights into the mechanisms driving specification and developmental trajectories of ovarian cells, they disrupt this crucial spatial context. To overcome this limitation, we used 10X Genomics Visium HD spatial transcriptomics to analyze the developing mouse ovary while maintaining its native cellular architecture. We captured all ovarian cell types at eight key fetal and postnatal timepoints, generating a near single cell resolution library of spatial gene expression across ovarian development. This comprehensive dataset allows analysis of dynamic transcriptional signatures associated with unique spatial patterning throughout development, including the establishment of cortex and medulla and assembly of ovarian follicles in each region. This dataset represents a fundamental resource for the investigation of regulatory mechanisms driving spatial patterning of the ovary and opens new avenues to explore the spatial determinants of female fertility and reproductive longevity.

Journal Article↗
PubMed2003

Spatial proximity of translocation-prone gene loci in human lymphomas.

Cancer cells frequently have disease-specific chromosome rearrangements. It is poorly understood why translocations between chromosomes recur at specific breakpoints in the genome. Here we provide evidence that higher-order spatial genome organization is a contributing factor in the formation of recurrent translocations. We show that MYC, BCL and immunoglobulin loci, which are recurrently translocated in various B-cell lymphomas, are preferentially positioned in close spatial proximity relative to each other in normal B cells. Loci in spatial proximity are non-randomly positioned towards the nuclear interior in normal B cells. This locus proximity is the consequence of higher-order genome structure rather than a property of individual genes. Our results suggest that the formation of specific translocations in human lymphomas, and perhaps other tissues, is determined in part by higher-order spatial organization of the genome.

DNA-Binding Proteins↗
PubMed2026

Striping artifact removal in VisiumHD data through nuclear counts modeling.

MOTIVATION: 10x Genomics VisiumHD enables spatial transcriptomics at 2 µm × 2 µm resolution but exhibits slide-specific, non-periodic striping artifacts due to lane-width variability. These multiplicative row/column effects distort bin total counts and can bias downstream analyses. The state-of-the-art destriping approach is the normalization procedure used as a preprocessing step in bin2cell; it applies sequential high-quantile row- then column-wise normalization, which is asymmetric and can introduce edge effects/macro-stripes and distortions of large-scale total-count structure. RESULTS: We propose a statistical destriping approach that leverages nuclei segmentation from the co-registered H&E image. Assuming transcript abundance is constant within each nucleus, we model bin counts with a negative binomial distribution whose mean is a product of a nucleus-specific concentration and row- and column-specific stripe-factors reflecting lane-width variation. We fit all parameters in a generalized linear modeling framework with cross-validated regularization on stripe-factors and iterative dispersion estimation, and use the fitted parameters to correct the observed counts into a destriped image. On synthetic data with known ground truth, our method improves stripe-factor estimation accuracy and reduces error in corrected counts relative to bin2cell and bin2cell-derived baselines. Across four public VisiumHD slides, it consistently lowers striping intensity while substantially better preserving biological signal present in the large-scale global count structure and avoiding the artifacts introduced by other methods. AVAILABILITY AND IMPLEMENTATION: All source code and links to publicly available data used for this study are available at https://github.com/paolamalsot/destriping-GLM.

Artifacts↗
PubMed2006

Genome-wide scanning of HoxB1-associated loci in mouse ES cells using an open-ended Chromosome Conformation Capture methodology.

Spatial proximity between genomic loci can play important roles in their function and regulation. We have developed an open-ended method based on Chromosome Conformation Capture technology allowing us to perform genome-wide scanning of the loci that form the spatial environment of a given locus at a given time. As a proof of principle we present the use of this methodology to investigate the dynamics of the spatial environment of the HoxB1 gene before and after the induction of its expression in mouse embryonic stem cells. Our results indicate that the HoxB1 locus' immediate spatial environment can be divided roughly into three parts: a first part is represented by a domain of immediate proximity on each side of the HoxB1 locus covering approximately 110 kb, a second part extends to a domain of 800 kb and a third part consists of distal intra-chromosomal and inter-chromosomal interactions. Consistent with FISH studies showing the decondensation and repositioning of HoxB1 outside of its chromosomal territory during its expression, the proportion of inter-chromosomal interactions between HoxB1 and the rest of the genome increases after its induction, while interactions with distal intra-chromosomal loci become less frequent. These results indicate that this technique can be used to determine the dynamics of loci interactions on a genome-wide scale.

Animals↗
PubMed2026

A divide and conquer strategy for recapitulating whole genome 3D structure using Hi-C data.

The three dimensional (3D) spatial organization of the genome is closely linked to biological functions and can be captured by Hi-C assays through interrogating genome-wide chromatin interactions. Methodologies for inferring 3D structures from Hi-C data summarized as a two-dimensional (2D) contact matrix can be broadly placed within the paradigms of optimization-based and sampling-based. Many optimization-based methods are capable of constructing whole genome 3D structures but do not account for spatial dependency in the 2D data matrix nor cell heterogeneity in bulk Hi-C data, which provide an average over millions of cells. Sampling-based methods, on the other hand, are probabilistic model-based and can account for not only dependency, heterogeneity, but also other features inherent in Hi-C data, such as over-dispersion and sparsity. However, whole-genome 3D structure recapitulation is too computationally expensive for sampling-based methods, while chromosome-by-chromosome strategies for sampling-based methods ignore important information on inter-chromosomal contacts. To address these issues, we propose the truncated Random effect EXpression-cut and paste (tREX-cap) method, which applies the tREX model within a divide and conquer strategy. The resulting method inherits the good data-feature-cognizant properties of tREX and, in the meantime, can efficiently infer the whole genome 3D structure. We demonstrate the performance of tREX-cap through an extensive simulation study and analyses of a Hi-C lymphoblastoid dataset and a Hi-C IMR90 dataset.

Humans↗
PubMed1998

Vitelline envelope genes of the yellow fever mosquito, Aedes aegypti.

Vitelline envelope genes from the mosquito Aedes aegypti were analyzed with respect to their DNA sequences, genomic representation, temporal and spatial expression profiles and response to 20-hydroxyecdysone. Genomic clones of three vitelline envelope genes, 15a-1, 15a-2 and 15a-3 were isolated. Southern analysis indicates that all three genes are represented by a single copy in the genome. The deduced amino acid sequences of all three vitelline envelope genes contain a conserved region of 46 residues that overlaps with a region that is conserved in four Drosophila melanogaster vitelline envelope genes. DNA was sequenced flanking the 15a-1, 15a-2 and 15a-3 coding regions. A 360 bp sequence 5' of the 15a-2 coding region was identified with 72% identity to a sequence upstream of the Ae. aegypti VgA1 vitellogenin gene. The temporal patterns of 15a-1, 15a-2 and 15a-3 expression, as determined by Northern analysis, were similar. The spatial patterns of expression, as determined by whole-mount in situ hybridization, differed between the three genes. 15a-1 and 15a-3 were only expressed in the middle and posterior regions of the follicle, while 15a-2 was also expressed at the anterior region. Vitelline envelope gene expression was higher in ovaries that were dissected at 0, 2 and 10 h following a blood meal and then incubated in vitro for 10 h in medium containing 10(-5) M 20-hydroxyecdysone, compared to ovaries that were incubated without hormone.

Aedes↗
PubMed2026

Nuclear DNA of plastid origin (NUPTs), neglected driver of genome variation and evolutionary innovation.

Plant nuclear genomes contain a variable, though typically minor, fraction of DNA sequences of plastid origin known as NUPTs. Unlike the massive transfer of DNA and genes from the proto-organelle genome to the nucleus that occurred during the endosymbiotic event that gave rise to plastids, the formation of NUPTs is an ongoing process that does not imply concomitant DNA loss. Although NUPTs are generally considered to be potentially deleterious insertions that are continuously generated and rapidly eliminated at near-constant turnover rates, accumulating evidence reveals alternative evolutionary trajectories. In this review, we discuss recent findings that highlight the episodic formation of NUPTs, their subsequent proliferation, and their eventual long-term fixation within the nuclear genome. We also explore their non-random spatial association with specific genomic elements. NUPTs show preferential overlap with specific superfamilies of transposable elements, which may facilitate their proliferation and dispersal throughout the nuclear genome. Regarding protein-coding genes, the contribution of NUPTs varies among species. In contrast, NUPTs are found to be consistently enriched among certain classes of non-coding RNA genes, notably rRNA, tRNA, and specific regulatory RNA families, suggesting that they are involved in the evolution of gene regulation and translational machinery. Overall, these findings underscore the unexpected complexity of the mechanisms underlying NUPT formation and support the idea that they are a significant source of genome variation and evolutionary innovation. Further research is necessary to fully elucidate the mechanisms underlying NUPT formation, as well as to determine their potential adaptive significance in plant genome evolution.

Plastids↗