Journal: Nature Genetics

Abbreviation

Nat Genet

Publisher

Nature

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1061-4036
1546-1718

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Publications1 - 10 of 40
  • An integrated transcriptomic cell atlas of human endoderm-derived organoids
    Item type: Journal Article
    Xu, Quan; Halle, Lennard; Hediyeh-zadeh, Soroor; et al. (2025)
    Nature Genetics
    Human pluripotent stem cells and tissue-resident fetal and adult stem cells can generate epithelial tissues of endodermal origin in vitro that recapitulate aspects of developing and adult human physiology. Here, we integrate single-cell transcriptomes from 218 samples covering organoids and other models of diverse endoderm-derived tissues to establish an initial version of a human endoderm-derived organoid cell atlas. The integration includes nearly one million cells across diverse conditions, data sources and protocols. We compare cell types and states between organoid models and harmonize cell annotations through mapping to primary tissue counterparts. Focusing on the intestine and lung, we provide examples of mapping data from new protocols and show how the atlas can be used as a diverse cohort to assess perturbations and disease models. The human endoderm-derived organoid cell atlas makes diverse datasets centrally available and will be valuable to assess fidelity, characterize perturbed and diseased states, and streamline protocol development.
  • Condensin I folds the Caenorhabditis elegans genome
    Item type: Journal Article
    Das, Moushumi; Semple, Jennifer I.; Haemmerli, Anja; et al. (2024)
    Nature Genetics
    The structural maintenance of chromosome (SMC) complexes – cohesin and condensins – are crucial for chromosome separation and compaction during cell division. During the interphase, mammalian cohesins additionally fold the genome into loops and domains. Here we show that, in Caenorhabditis elegans, a species with holocentric chromosomes, condensin I is the primary, long-range loop extruder. The loss of condensin I and its X-specific variant, condensin I^DC, leads to genome-wide decompaction, chromosome mixing and disappearance of X-specific topologically associating domains, while reinforcing fine-scale epigenomic compartments. In addition, condensin I/I^DC inactivation led to the upregulation of X-linked genes and unveiled nuclear bodies grouping together binding sites for the X-targeting loading complex of condensin I^DC. C. elegans condensin I/I^DC thus uniquely organizes holocentric interphase chromosomes, akin to cohesin in mammals, as well as regulates X-chromosome gene expression.
  • Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease
    Item type: Journal Article
    Lambert, Jean-Charles; Ibrahim-Verbaas, Carla A.; Harold, Denise; et al. (2013)
    Nature Genetics
  • Reconstructing de novo silencing of an active plant retrotransposon
    Item type: Journal Article
    Marí Ordóñez, Arturo; Marchais, Antonin; Etcheverry, Mathilde; et al. (2013)
    Nature Genetics
  • Unraveling tumor--immune heterogeneity in advanced ovarian cancer uncovers immunogenic effect of chemotherapy
    Item type: Journal Article
    Jiménez-Sánchez, Alejandro; Cybulska, Paulina; Mager, Katherine LaVigne; et al. (2020)
    Nature Genetics
    In metastatic cancer, the degree of heterogeneity of the tumor microenvironment (TME) and its molecular underpinnings remain largely unstudied. To characterize the tumor–immune interface at baseline and during neoadjuvant chemotherapy (NACT) in high-grade serous ovarian cancer (HGSOC), we performed immunogenomic analysis of treatment-naive and paired samples from before and after treatment with chemotherapy. In treatment-naive HGSOC, we found that immune-cell-excluded and inflammatory microenvironments coexist within the same individuals and within the same tumor sites, indicating ubiquitous variability in immune cell infiltration. Analysis of TME cell composition, DNA copy number, mutations and gene expression showed that immune cell exclusion was associated with amplification of Myc target genes and increased expression of canonical Wnt signaling in treatment-naive HGSOC. Following NACT, increased natural killer (NK) cell infiltration and oligoclonal expansion of T cells were detected. We demonstrate that the tumor–immune microenvironment of advanced HGSOC is intrinsically heterogeneous and that chemotherapy induces local immune activation, suggesting that chemotherapy can potentiate the immunogenicity of immune-excluded HGSOC tumors.
  • A genomic variation map provides insights into the genetic basis of cucumber domestication and diversity
    Item type: Journal Article
    Qi, Jianjian; Liu, Xin; Shen, Di; et al. (2013)
    Nature Genetics
  • Meta-analysis of genome-wide association studies for cattle stature identifies common genes that regulate body size in mammals
    Item type: Journal Article
    Bouwman, Aniek C.; Daetwyler, Hans D.; Chamberlain, Amanda J.; et al. (2018)
    Nature Genetics
    Stature is affected by many polymorphisms of small effect in humans1. In contrast, variation in dogs, even within breeds, has been suggested to be largely due to variants in a small number of genes2,3. Here we use data from cattle to compare the genetic architecture of stature to those in humans and dogs. We conducted a meta-analysis for stature using 58,265 cattle from 17 populations with 25.4 million imputed whole-genome sequence variants. Results showed that the genetic architecture of stature in cattle is similar to that in humans, as the lead variants in 163 significantly associated genomic regions (P < 5 × 10−8) explained at most 13.8% of the phenotypic variance. Most of these variants were noncoding, including variants that were also expression quantitative trait loci (eQTLs) and in ChIP–seq peaks. There was significant overlap in loci for stature with humans and dogs, suggesting that a set of common genes regulates body size in mammals.
  • Chromosome-scale genome assembly provides insights into rye biology, evolution and agronomic potential
    Item type: Journal Article
    Rabanus-Wallace, M. Timothy; Mascher, Martin; Lux, Thomas; et al. (2021)
    Nature Genetics
    Rye (Secale cereale L.) is an exceptionally climate-resilient cereal crop, used extensively to produce improved wheat varieties via introgressive hybridization and possessing the entire repertoire of genes necessary to enable hybrid breeding. Rye is allogamous and only recently domesticated, thus giving cultivated ryes access to a diverse and exploitable wild gene pool. To further enhance the agronomic potential of rye, we produced a chromosome-scale annotated assembly of the 7.9-gigabase rye genome and extensively validated its quality by using a suite of molecular genetic resources. We demonstrate applications of this resource with a broad range of investigations. We present findings on cultivated rye’s incomplete genetic isolation from wild relatives, mechanisms of genome structural evolution, pathogen resistance, low-temperature tolerance, fertility control systems for hybrid breeding and the yield benefits of rye–wheat introgressions.
  • Breast tumor microenvironment structures are associated with genomic features and clinical outcome
    Item type: Journal Article
    Danenberg, Esther; Bardwell, Helen; Zanotelli, Vito R.T.; et al. (2022)
    Nature Genetics
    The functions of the tumor microenvironment (TME) are orchestrated by precise spatial organization of specialized cells, yet little is known about the multicellular structures that form within the TME. Here we systematically mapped TME structures in situ using imaging mass cytometry and multitiered spatial analysis of 693 breast tumors linked to genomic and clinical data. We identified ten recurrent TME structures that varied by vascular content, stromal quiescence versus activation, and leukocyte composition. These TME structures had distinct enrichment patterns among breast cancer subtypes, and some were associated with genomic profiles indicative of immune escape. Regulatory and dysfunctional T cells co-occurred in large ‘suppressed expansion’ structures. These structures were characterized by high cellular diversity, proliferating cells and enrichment for BRCA1 and CASP8 mutations and predicted poor outcome in estrogen-receptor-positive disease. The multicellular structures revealed here link conserved spatial organization to local TME function and could improve patient stratification.
  • The Ruminant Telomere-to-Telomere (RT2T) Consortium
    Item type: Journal Article
    Kalbfleisch, Theodore S.; McKay, Stephanie D.; Murdoch, Brenda M.; et al. (2024)
    Nature Genetics
    Telomere-to-telomere (T2T) assemblies reveal new insights into the structure and function of the previously ‘invisible’ parts of the genome and allow comparative analyses of complete genomes across entire clades. We present here an open collaborative effort, termed the ‘Ruminant T2T Consortium’ (RT2T), that aims to generate complete diploid assemblies for numerous species of the Artiodactyla suborder Ruminantia to examine chromosomal evolution in the context of natural selection and domestication of species used as livestock.
Publications1 - 10 of 40