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Transitional liver progenitor cells (TLPCs), which derive from biliary epithelial cells (BECs), differentiate into hepatocytes after serious liver damage. Notch and WNT/β-catenin signaling regulate BEC-to-TLPC and TLPC-to-hepatocyte conversions, respectively.
Premalignant stromal cells from women with germline BRCA1 mutations exhibit increased expression of secreted factors regulating epithelial homeostasis in a paracrine fashion. These secreted factors, such as MMP3, promote premalignant epithelial changes including elevated proliferation and altered differentiation of a subpopulation of luminal progenitor cells.
A cross-ancestry genomic and transcriptomic cohort of gastric cancer highlights significantly mutated genes and mutational signatures, some of which are ancestry-specific.
Immune dN/dS is the ratio of nonsynonymous to synonymous mutations in the MHC-bound immunopeptidome. Application of immune dN/dS to cancer datasets shows that it distinguishes immune evasion and escape and predicts response to immunotherapies.
The canonical BRG1/BRM-associated factor (cBAF) complex is recruited by HNF1A/B to angiotensin-converting enzyme 2 (ACE2) enhancers, promoting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Inhibition of the catalytic activity of SMARCA4 precludes ACE2 expression and reduces susceptibility to SARS-CoV-1 and major SARS-CoV-2 variants.
A graph-based pan-genome constructed using de novo genome assemblies of ten pearl millet accessions adapted to different climates worldwide identifies structural variations and their contribution to heat tolerance in pearl millet.
MERVL transcripts, but not MERVL-encoded proteins, are essential for mouse preimplantation development. Depletion of MERVL RNA perturbs early lineage specification and leads to increased chromatin accessibility at, and transcription of, two-cell-specific genes.
Arabidopsis sperm cells exhibit widespread chromatin bivalency. Incorporation of histone variant H3.10 regulates sperm chromatin identity. In contrast, in vegetative cells, repressed genes are marked by H3K27me3, while pollination-related genes are active and marked by broad H3K4me3 domains.
Multiple samples collected at autopsy from women with homologous recombination-deficient high-grade serous ovarian cancer highlight substantial inter- and intratumoral heterogeneity. A plethora of resistance mechanisms were identified within and between patients.
Network expansion of trait-associated genes for 1,002 human phenotypes identifies pleiotropic gene modules and biological processes associated with multiple traits, and potential opportunities for drug repurposing and development.
High-quality genome assembly of a prominent drought-resistant maize germplasm CIMBL55 and genetic variation analyses provide a resource for genetic dissection and result in the improvement of maize drought resistance.
The identification of genes and enhancers associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) in women highlights variants within Alu retrotransposons. The WHRadjBMI-linked gene SNX10 plays a role in human adipocyte differentiation and diet-induced adipose expansion in female mice.
Genetic manipulation of the Sox2 locus in mice shows that gene activation by distal enhancers does not require CTCF-mediated loops and can occur across ectopic CTCF-mediated boundaries. The ability to bypass CTCF boundaries varies with their insulation strength and the tissue-specific enhancers responsible for activation.
Whole-genome sequencing of healthy human epithelial crypts from the small intestines of 39 individuals highlights APOBEC enzymes as a common contributor to the overall mutational burden in this tissue.
A multi-ancestry transcriptome-wide association study using an optimal linear combination of association statistics provides insights into tobacco use biology and suggests opportunities for drug repurposing.
Genome-wide analyses identify 27 loci associated with attention-deficit hyperactivity disorder and provide insights into its genetic architecture in relation to other psychiatric disorders and cognitive traits.
Genome-wide analyses in BioBank Japan and populations of European ancestry identify new risk loci for atrial fibrillation. A polygenic risk score constructed from the cross-ancestry meta-analysis is associated with increased risk of long-term cardiovascular mortality.
A high-quality Ixodes scapularis genome contributes to improved annotations, expansion of gene families, development of proteome catalogs and the deciphering of genetic variation in wild ticks.
Notch1 mutations have opposing effects on clonal growth in normal and tumor cells of the mouse esophagus. In a mouse model of squamous esophageal tumorigenesis, Notch1 blockade reduced premalignant tumor growth, suggesting that it might be an effective prevention strategy for the disease.