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Results for “Single cell transcriptomics”

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At least 523 records · Page 29Linked to original sources

PubMed2026

CARS1 as a Prognostic Biomarker and Candidate Therapeutic Vulnerability in Hepatocellular Carcinoma: Insights Into Tumor Progression and the Immune Microenvironment.

BACKGROUND: Cysteinyl-tRNA synthetase 1 (CARS1) has been included in ferroptosis-related prognostic signatures, but its clinicopathological relevance, cellular functions, and relationship with the immune microenvironment in hepatocellular carcinoma (HCC) remain incompletely characterized. METHODS: Transcriptomic and clinical data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset were integrated with corresponding data from an institutional HCC tissue cohort of 60 patients. CARS1 expression was evaluated by immunohistochemistry, and immune infiltration was examined using single-sample gene-set enrichment analysis (ssGSEA) and multiplex immunofluorescence, as well as by analyzing public single-cell datasets. The effects of CARS1 depletion were evaluated in MHCC97H and Hep3B cells using Cell Counting Kit-8 (CCK-8) assays, cell-cycle profiling, wound-healing assays, Transwell migration assays, western blotting, and erlotinib-sensitivity assays. RESULTS: CARS1 expression was elevated in HCC and was associated with adverse clinicopathological features and poor overall survival. Quantitative immunohistochemistry confirmed elevated CARS1 protein expression in tumor tissues. CARS1 depletion inhibited cell proliferation, altered cell-cycle distribution, impaired migration, and enhanced in vitro sensitivity to erlotinib. High CARS1 expression was also associated with increased infiltration of Th2-like immune cells. CONCLUSIONS: Elevated CARS1 expression is associated with an adverse biological and immune phenotype in HCC. These clinical, histopathological, and loss-of-function findings support further investigation of CARS1 as a prognostic marker and candidate therapeutic target in HCC, although additional mechanistic and in vivo validation is required.

Humans↗

PubMed2025

Epstein-Barr Virus-Associated Gastric Cancer: A Histopathologic Study With Comprehensive Molecular Profiling.

A subset of gastric cancers (GCs) is linked to Epstein-Barr virus (EBV) infection. This study aims to characterize the histopathological and molecular features of EBV-associated GCs (EBVaGCs), focusing on predictive biomarkers and genomic and transcriptomic analysis. A total of 35 primary EBVaGCs were considered. The presence of EBV was confirmed with in situ hybridization. Immunohistochemical analyses for HER2, PD-L1, claudin 18.2, and mismatch repair proteins were performed. Genomic and transcriptomic profiles were assessed using AmoyDx Master Panel, which can identify single-nucleotide variants, InDels, and copy number variations on 571 hot genes, as well as microsatellite status, tumor molecular burden, and homologous recombination deficiency at the DNA level; however, at the RNA level, it identifies rearrangements/fusions in 45 genes and also quantifies the expression of 2396 cancer-related transcripts. The following histotypes were identified: carcinoma with lymphoid stroma (CLS; 69%), tubular (20%), and mixed (11%). Most cases were associated with atrophic gastritis (71%), and only 11% with dysplasia. The vast majority (94%) of EBVaGCs expressed EBV-encoded RNA in all tumor cells. Mismatch repair deficiency and HER2 overexpression were each observed in 6% of cases, whereas all tumors had a PD-L1-combined positive score ≥10. Sixty-six percent of cases showed moderate/strong claudin 18.2 expression in ≥75% of cancer cells. The most frequently altered genes were PIK3CA (41%) and ARID1A (17%). Transcriptomic analysis revealed substantial differential gene expression between EBVaGCs and EBV-negative controls, with upregulation of genes involved in antigen presentation, natural killer cell-mediated cytotoxicity, and cytokine-cytokine receptor interaction in EBVaGCs. Within EBVaGC, CLS showed higher expression of immune-related transcripts and higher PD-L1 expression than other histotypes. This study establishes EBVaGC as a distinct molecular class, with a distinctive profile of genomic alterations and expression of predictive biomarkers, and also with a unique immune microenvironment with enhanced cytotoxic activity. The findings highlight EBV's role in early tumor development and EBVaG-CLS as a distinct subgroup within EBVaGC, characterized by unique morphologic features and a pronounced immune activation profile.

Humans↗

PubMed2026

Characterization of METTL3/14-mediated m6A modification in human transcriptome using Nanopore direct RNA sequencing.

Post-transcriptional RNA modifications modulate diverse aspects of RNA metabolism. N6-methyladenosine (m6A), one of the most abundant internal RNA modifications, is deposited by the core methyltransferase complex, METTL3 and METTL14. Oxford Nanopore Technologies (ONT) platform permits direct, single RNA molecule sequencing while preserving native modifications. However, without rigorous benchmarking, the accuracy and reproducibility of modification detection remain uncertain. Here, we leveraged ONT to comprehensively profile bona fide m6A modifications in cellular RNAs at single-nucleotide resolution by integrating two direct RNA sequencing chemistries (RNA002 and RNA004) with the m6Anet and Dorado modification-detection models. We independently depleted METTL3 and METTL14 in human cells and rigorously validated modification calls through several assays and independent orthogonal methods (GLORI and miCLIP). We find that Dorado detected a higher number of m6A events and enabled simultaneous detection of other RNA modifications (5-methylcytosine, pseudouridine, and inosine). Pairing Dorado with an in vitro transcribed, unmodified control under stringent filtering, we provide compelling evidence supporting a global reduction in m6A sites and stoichiometry within coding sequences and across genes, particularly in highly modified genes and sites, and at consensus DRACH motifs. We report a differential and complex regulation of modified transcripts, accompanied by a global reduction in poly(A) tail length. Notably, METTL3 and METTL14 depletion produced distinct transcript-specific effects, supporting non-redundant roles within the m6A writer complex. Together, our study illustrates a notable advancement of ONT capabilities and establishes a robust transcriptome-wide framework for RNA modification detection, thereby laying the groundwork for exploring the contribution of METTL3/METTL14 to cellular functions and disease.

Humans↗

PubMed2026

Myeloma engraftment suppresses osteocytic ossification signatures rescued by loading in mice and reveals predictors of patient outcome.

Multiple myeloma (MM) is a malignant plasma cell disease inducing osteolytic lesions by disrupting bone homeostasis, fostering catabolic and suppressing anabolic functions. While the impact on osteoblast generation and function is well documented, alterations of osteocyte function and extracellular matrix (ECM) are not yet fully understood. Thus, using a syngeneic mouse model of MM by injecting MOPC315.BM cells intratibially into BALB/c mice (n = 95), we performed transcriptomic profiling of an osteocyte-enriched population and identified a mechanosensitive matrisomal gene signature, which was disrupted by tumor engraftment. Non-invasive tibial loading restored the expression of 94 ECM-associated genes, including collagens, fibronectin, and aggrecan. Cross-species integration with RNA-seq data from 387 MM patients revealed eight ECM-related genes whose expression correlated with overall survival (VEGFA, BCAN, FGF13, TNFSF8, SDC1, LAMC1, SEMA3A, and CCL2). Four of these genes (Vegfa, Sdc1, Sema3a, Ccl2) were also load-responsive in a murine osteocyte (IDG-SW3 cells) bioreactor model. Our findings indicate that an existing mechanosensitive osteocytic repair program is suppressed by MM cells, which can be reinvigorated via a brief single loading session. It suggests that exercise-based interventions may be beneficial to restore bone mass through endochondral ossification programs in patients with MM.

Bone disease↗

PubMed2006

Identification of candidate maternal-effect genes through comparison of multiple microarray data sets.

Transcriptional profiling by microarray hybridization has become a standard method to analyze global gene expression and has resulted in the availability of enormous amounts of experimental data. Given the number of different microarray platforms currently in use, it is critical to determine how reproducible results are from one platform to another. Additional variability may also arise from tissue collection and protocol differences among laboratories. In an effort to identify genes whose maternal mRNA pools are critical during preimplantation development, we compared published results of three independent studies of the mouse preimplantation embryo transcriptome, each performed in a different laboratory using different microarray platforms. We searched the combined data set for genes whose expression patterns were consistent among the three experiments. Querying for presence or absence at single developmental windows indicates that between 52% and 60% of genes are in agreement among the three experiments. Searching for expression patterns across three developmental windows (oocyte + 1-cell, 2- through 8-cell, and blastocyst stage) revealed approximately 33% agreement among the three experiments, although the majority of these genes were either always present or always absent. Using this approach, we identified 51 genes with a predicted expression pattern of maternal RNA only (not present during 2-cell through 8-cell or at the blastocyst stage). RT-PCR validation indicates 37 (72%) of these candidates have the microarray-predicted expression pattern and represent candidate maternal-effect genes. Based on our analysis, we conclude that data mining microarray experiments in this way greatly enhances candidate gene expression pattern accuracy.

Animals↗

PubMed2004

Transcriptome analysis of early chondrogenesis in ATDC5 cells induced by bone morphogenetic protein 4.

We performed serial analysis of gene expression (SAGE) profiling in mouse chondrogenic ATDC5 cells before and 6 h after the onset of chondrogenesis induced by BMP4. A total of 43,656 SAGE tags (21,875 and 21,781 tags from the uninduced and induced libraries, respectively) were analyzed. Our analysis predicted that 139 transcripts were differentially represented in the two libraries (p < 0.05), including 72 downregulated and 67 upregulated transcripts. Ninety-five of them matched single UniGene entries (77 known genes and 18 ESTs), while 12 tags corresponded to potentially novel genes. Surprisingly, many of these known genes have never been implicated in chondrogenic differentiation. Interestingly, we found that a significant fraction of these genes formed physical linkage groups. This suggests that the transcriptional control by BMP signaling is in part targeted to genes in certain chromosomal domains. Together, our results provide novel insights into molecular events regulated by BMP signaling in chondrogenesis.

Animals↗

PubMed2004

Functional genomics of cell elongation in developing cotton fibers.

Cotton fibers are single-celled seed trichomes of major economic importance. Factors that regulate the rate and duration of cell expansion control fiber morphology and important agronomic traits. For genetic characterization of rapid cell elongation in cotton fibers, approximately 14,000 unique genes were assembled from 46,603 expressed sequence tags (ESTs) from developmentally staged fiber cDNAs of a cultivated diploid species ( Gossypium arboreum L.). Conservatively, the fiber transcriptome represents 35-40% of the genes in the cotton genome. In silico expression analysis revealed that rapidly elongating fiber cells exhibit significant metabolic activity, with the bulk of gene transcripts, represented by three major functional groups - cell wall structure and biogenesis, the cytoskeleton and energy/carbohydrate metabolism. Oligonucleotide microarrays revealed dynamic changes in gene expression between primary and secondary cell wall biogenesis showing that fiber genes in the dbEST are highly stage-specific for cell expansion - a conclusion supported by the absence of known secondary cell wall-specific genes from our fiber dbEST. During the developmental switch from primary to secondary cell wall syntheses, 2553 "expansion-associated" fiber genes are significantly down regulated. Genes (81) significantly up-regulated during secondary cell wall synthesis are involved in cell wall biogenesis and energy/carbohydrate metabolism, which is consistent with the stage of cellulose synthesis during secondary cell wall modification in developing fibers. This work provides the first in-depth view of the genetic complexity of the transcriptome of an expanding cell, and lays the groundwork for studying fundamental biological processes in plant biology with applications in agricultural biotechnology.

Cell Growth Processes↗

PubMed2024

Novel Genetic Loci in Early-Onset Gout Derived From Whole-Genome Sequencing of an Adolescent Gout Cohort.

OBJECTIVE: Mechanisms underlying the adolescent-onset and early-onset gout are unclear. This study aimed to discover variants associated with early-onset gout. METHODS: We conducted whole-genome sequencing in a discovery adolescent-onset gout cohort of 905 individuals (gout onset 12 to 19 years) to discover common and low-frequency single-nucleotide variants (SNVs) associated with gout. Candidate common SNVs were genotyped in an early-onset gout cohort of 2,834 individuals (gout onset ≤30 years old), and meta-analysis was performed with the discovery and replication cohorts to identify loci associated with early-onset gout. Transcriptome and epigenomic analyses, quantitative real-time polymerase chain reaction and RNA sequencing in human peripheral blood leukocytes, and knock-down experiments in human THP-1 macrophage cells investigated the regulation and function of candidate gene RCOR1. RESULTS: In addition to ABCG2, a urate transporter previously linked to pediatric-onset and early-onset gout, we identified two novel loci (Pmeta < 5.0 × 10-8): rs12887440 (RCOR1) and rs35213808 (FSTL5-MIR4454). Additionally, we found associations at ABCG2 and SLC22A12 that were driven by low-frequency SNVs. SNVs in RCOR1 were linked to elevated blood leukocyte messenger RNA levels. THP-1 macrophage culture studies revealed the potential of decreased RCOR1 to suppress gouty inflammation. CONCLUSION: This is the first comprehensive genetic characterization of adolescent-onset gout. The identified risk loci of early-onset gout mediate inflammatory responsiveness to crystals that could mediate gouty arthritis. This study will contribute to risk prediction and therapeutic interventions to prevent adolescent-onset gout.

Humans↗

PubMed2004

Prototypic T cell receptor and CD4-like coreceptor are expressed by lymphocytes in the agnathan sea lamprey.

All jawed vertebrates have highly diverse lymphocyte receptors, which allow discrimination between self and nonself antigens as well as the recognition of potential pathogens. Key elements of the anticipatory recombinatorial immune system in jawed vertebrates are the TCR, Ig, and MHC genes, but their ancestral genes have not been found in more basal vertebrates. In this study, we extended our analysis of the transcriptome of lymphocyte-like cells in the lamprey to identify the TCR-like and CD4-like genes. The structural features of these genes and their preferential expression in lymphocytes make them attractive candidates for ancestral TCR and CD4 genes. The TCR-like gene contains both V (variable) and J (joining) sequences in its first exon and exists as a single-copy gene that is invariant. Thus, the TCR-like gene cannot account for the receptor diversity that is required for the immune responses reported for lamprey, but it could have been easily modified to serve as an evolutionary precursor of modern TCR and Ig genes.

Amino Acid Sequence↗

PubMed2005

New aspects of laser microdissection in research and routine.

Laser microdissection has opened a window to new technologies. The scientific fields of genomics, transcriptomics, and proteomics need pure samples for rendering reliable results. Homogeneous sample preparation is a prerequisite for modern molecular analyses, both qualitative and quantitative. Laser microdissection and pressure catapulting (LMPC) is a tool for isolating specific cells from complex tissues in a non-contact and contamination-free manner. Because LMPC technology is an optimal method for obtaining fast and reliable access to single cells, the possibility of automatic isolation of single fetal cells has the promise of being a big step forward in developing protocols for non-invasive prenatal diagnosis.

Animals↗

PubMed2025

Longitudinal multi-omics in alpha-synuclein Drosophila model discriminates disease- from age-associated pathologies in Parkinson's disease.

Parkinson's disease (PD) starts decades before symptoms appear, usually in the later decades of life, when age-related changes are occurring. To identify molecular changes early in the disease course and distinguish PD pathologies from aging, we generated Drosophila expressing alpha-synuclein (αSyn) in neurons and performed longitudinal bulk transcriptomics and proteomics on brains at six time points across the lifespan and compared the data to healthy control flies as well as human post-mortem brain datasets. We found that translational and energy metabolism pathways were downregulated in αSyn flies at the earliest timepoints; comparison with the aged control flies suggests that elevated αSyn accelerates changes associated with normal aging. Unexpectedly, single-cell analysis at a mid-disease stage revealed that neurons upregulate protein synthesis and nonsense-mediated decay, while glia drive their overall downregulation. Longitudinal multi-omics approaches in animal models can thus help elucidate the molecular cascades underlying neurodegeneration vs. aging and co-pathologies.

Journal Article↗

PubMed2026

Maize ZmMYB59 inhibits post-germinative shoot and root elongation through ZmGA2ox3/10-mediated gibberellin catabolism.

Gibberellin (GA) promotes seed germination, but sustained or excessive GA signaling after germination can lead to aberrant root and shoot elongation. How GA homeostasis is transcriptionally restrained during post-germinative seedling development remains unclear. Using overexpression and gene-edited maize materials, we demonstrate that ZmMYB59 inhibits root and shoot elongation during post-germinative growth. Integrated RNA-Seq and CUT&Tag analyses identified the GA catabolism genes ZmGA2ox3 and ZmGA2ox10 as candidate direct targets of ZmMYB59. Hormone profiling analysis showed elevated bioactive GA1 and GA4 levels in the scutellum and aleurone layer cells of zmmyb59 mutants. Dual-luciferase assays, electrophoretic mobility shift assays, and ChIP-qPCR further confirmed that ZmMYB59 directly binds AC8 cis-elements in the ZmGA2ox3/10 promoters and activates their transcription. The zmga2ox3/10 double mutant, but neither single mutant, exhibited enhanced root and shoot elongation, accompanied by GA4 accumulation. This phenotype was suppressed by exogenous application of the GA biosynthesis inhibitor uniconazole. Transcriptomic and biochemical analyses further revealed enhanced starch degradation, reduced starch content, and increased soluble sugar accumulation in the double mutant. Taken together, these findings reveal that the ZmMYB59-ZmGA2ox3/10 module restrains GA accumulation and starch mobilization after germination, thereby coordinating reserve utilization with post-germinative root and shoot growth in maize.

Gibberellins↗

PubMed2026

Strategies for mosaic variant calling in brain disorders.

The human brain is a genomic mosaic, where postzygotic mutations arising from embryogenesis to senescence drive diverse neurodevelopmental and neurodegenerative diseases. Because of numerous sequencing artifacts at ultralow variant allele frequencies (VAFs), detecting these variants remains a significant analytical challenge. This review focuses on single-nucleotide variants and small indels, summarizing current strategies for aligning sampling methods, including bulk, laser capture microdissection, and single-cell genomics, with the expected clonal architecture of the brain. It emphasizes that mosaic detection sensitivity is fundamentally constrained by sequencing depth, since even the most advanced algorithms cannot identify variants not physically represented in the sequencing library. The review further recommends the selection of variant calling algorithms based on validated VAF detection performance, matching tools like MuTect2 and MosaicForecast to their optimal performance ranges. Furthermore, we discuss how multitissue sampling, as emphasized by the SMaHT project, addresses the matched-control dilemma and supports accurate variant classification via cross-tissue VAF gradients. Integrating these established pipelines with multiomics modalities, including transcriptomic and epigenetic data, could advance the field toward a functional understanding of how the somatic genome impacts human brain health and disease.

Humans↗

PubMed2026

Cell-of-origin Discovery in Infant Leukemia through Integration of 3D Models and Patient Transcriptomic Data.

Pediatric hematological malignancies remain challenging to investigate and model due to the age group-specificity of certain genetic abnormalities. In utero origin has been demonstrated for a subset of pediatric leukemias, placing their respective cell of origin (CoO) during embryonic development. We recently reported a 3D hemogenic gastruloid (haemGx) model of embryonic blood formation derived from mouse embryonic stem cells, resolving the spatio-temporal complexity of developmental hematopoiesis. Importantly, it allows genetic engineering to introduce disease-relevant mutations. Using haemGx, we modeled the most common acute myeloid leukemia exclusive to infants (infAML), subtype t(7;12)(q36;p13), which arises in utero and is characterized by MNX1 overexpression. Here, we detail a method to define susceptibility to specific mutations that integrate phenotypic and transcriptional changes in the haemGx system and compares them with patient data. By proxy of our MNX1-overexpression haemGx, we show a pipeline from cell engineering to downstream analyses of leukemogenic potential. In particular, we focus on the clinical relevance of the model by integrating single-cell and/or bulk RNA sequencing from the haemGx platform with patient data to extract cellular composition and temporal placement of the putative CoO. This method is adaptable to the introduction of other oncogenic mutations, chromosomal rearrangements, or epigenetic modifications, as well as to chemical perturbations, including drug vulnerability and growth factor dependence. This flexibility allows for broad application across diverse disease contexts, enabling mechanistic dissection of how specific alterations disrupt early developmental trajectories with clinical relevance.

Humans↗

PubMed2004

Generation of longer 3' cDNA fragments from massively parallel signature sequencing tags.

Massively Parallel Signature Sequencing (MPSS) is a powerful technique for genome-wide gene expression analysis, which, similar to SAGE, relies on the production of short tags proximal to the 3'end of transcripts. A single MPSS experiment can generate over 10(7) tags, providing a 10-fold coverage of the transcripts expressed in a human cell. A significant fraction of MPSS tags cannot be assigned to known transcripts (orphan tags) and are likely to be derived from transcripts expressed at very low levels (approximately 1 copy per cell). In order to explore the potential of MPSS for the characterization of the human transcriptome, we have adapted the GLGI protocol (Generation of Longer cDNA fragments from SAGE tags for Gene Identification) to convert MPSS tags into their corresponding 3' cDNA fragments. GLGI-MPSS was applied to 83 orphan tags and 41 cDNA fragments were obtained. The analysis of these 41 fragments allowed the identification of novel transcripts, alternative tags generated from polymorphic and alternatively spliced transcripts, as well as the detection of artefactual MPSS tags. A systematic large-scale analysis of the genome by MPSS, in combination with the use of GLGI-MPSS protocol, will certainly provide a complementary approach to generate the complete catalog of human transcripts.

Alternative Splicing↗

PubMed2026

Early oligodendrocyte dysfunction signature in Alzheimer's disease: Insights from DNA methylomics and transcriptomics.

Much research into the aetiology of Alzheimer's disease (AD) has focused on neuronal cell types, while studies on the contribution of glial cells, particularly oligodendrocytes (OLGs), are only starting to emerge. Altered brain DNA methylation, an epigenetic modification that provides the interplay between genetics and environmental cues to tightly regulate gene expression, is well documented in AD. Yet, cell-type-specific investigations remain limited. Here, we examine the role of DNA methylation and OLGs in AD, and how such changes may impact gene expression. We performed weighted-gene correlation network analysis (WGCNA) on multiple brain omics AD datasets across species: human DNA methylation data from 4 brain regions, human brain single-nuclei RNA sequencing data and mouse brain RNA sequencing data. We compared AD-associated network modules enriched for OLG genes across AD brain regions, as well as with other neurodegenerative disease DNA methylation datasets. We identified a DNA methylation signature associated with AD, enriched for OLGs, and preserved across brain regions representing early and late AD pathology stages. Genes within this signature showed altered expression in AD OLGs, confirming cell-type specificity and relevance to AD. This OLG signature was also preserved in transgenic mice with early Aβ pathology and in other neurodegenerative diseases without Aβ pathology. We reveal a consistent pattern of OLG dysfunction spanning early to late stages of AD, across DNA methylation and gene expression. Our findings highlight OLG-associated DNA methylation changes as important in AD pathogenesis, and possibly in other neurodegenerative diseases, opening new avenues for therapeutic development.

Alzheimer Disease↗

PubMed2024

eQTLs identify regulatory networks and drivers of variation in the individual response to sepsis.

Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by a dysregulated response to infection, for which disease heterogeneity is a major obstacle to developing targeted treatments. We have previously identified gene-expression-based patient subgroups (sepsis response signatures [SRS]) informative for outcome and underlying pathophysiology. Here, we aimed to investigate the role of genetic variation in determining the host transcriptomic response and to delineate regulatory networks underlying SRS. Using genotyping and RNA-sequencing data on 638 adult sepsis patients, we report 16,049 independent expression (eQTLs) and 32 co-expression module (modQTLs) quantitative trait loci in this disease context. We identified significant interactions between SRS and genotype for 1,578 SNP-gene pairs and combined transcription factor (TF) binding site information (SNP2TFBS) and predicted regulon activity (DoRothEA) to identify candidate upstream regulators. Overall, these approaches identified putative mechanistic links between host genetic variation, cell subtypes, and the individual transcriptomic response to infection.

Humans↗

PubMed2025

Genome topology analysis and transcriptomics of human osteoclasts reveals enhancer-promoter interactions at loci for bone traits and diseases.

Genome-wide association studies (GWAS) relevant to osteoporosis have identified hundreds of loci; however, understanding how these variants influence the phenotype is complicated because most reside in non-coding DNA sequence that serves as transcriptional enhancers and repressors. To advance knowledge on these regulatory elements in osteoclasts (OCs), we performed Micro-C analysis, which informs on the genome topology of these cells and integrated the results with transcriptome and GWAS data to further define loci linked to BMD. Using blood cells isolated from 4 healthy participants aged 31-61 yr, we cultured OC in vitro and generated a Micro-C chromatin conformation capture dataset. We characterized chromatin loops (CLs) in OC from among more than 69 million chromatin interactions identified in the genome. Of the CL identified in OC, >16 000 were unique compared to precursor cells. When sentinel single nucleotide polymorphisms from osteoporosis and bone-related GWAS and those in linkage disequilibrium at r 2 > 0.6 were mapped to CL for OC, 12 588 of these variants were observed within chromatin contact regions. Notable in differential gene ontology enrichment analyses of the topology data for OC and precursors were pathways regulating pluripotency of stem cells, Wnt signaling, nucleotide-binding oligomerization domain (NOD)-like receptor signaling and chemokine signaling. These data, in combination with other 3D genome architecture and epigenetic data (eg, histone modifications and chromatin accessibility), will be useful in modeling to predict genome-wide, which enhancers regulate which genes in OC. This data will therefore also be informative for resolving GWAS hits. In conclusion, we have generated a high-resolution genome topology dataset for human OC and have used this to identify CLs relevant to studies of the genetics of osteoporosis. This data will serve as a powerful resource to inform future functional studies of OC biology.

BMD↗