Research Briefing

How histone modifications are reprogrammed through germline development in plants is poorly understood. We found that H3K27me3 and H3K4me3 are extensively reprogrammed throughout the development of Arabidopsis male gametophyte. This reprogramming leads to widespread chromatin bivalency and selective removal of H3K27me3 marks from key developmental regulators in sperm.

We introduce molecular and cellular criteria — based on morphology, ploidy, CpG island methylation and immune infiltration — that improve the characterization of malignant pleural mesothelioma. These criteria reveal adaptation strategies that are adopted by tumor cells and offer new possibilities for classification and clinical management.

The expression of murine endogenous retrovirus-L (MERVL) is transiently upregulated at the two-cell stage in mouse embryos, coinciding with zygotic genome activation and the acquisition of totipotency; however, its role in embryogenesis remains elusive. We show that nuclear expression of MERVL is required for accurate regulation of the host transcriptome and chromatin state during preimplantation development.

Interacting proteins commonly perform similar functions. A protein interaction network analysis of genes linked to 1,002 human traits identifies molecular mechanisms that are shared across traits and so-called pleiotropic biological processes, whose disruption might affect many aspects of human biology.

A meta-analysis of harmonized human brain RNA-seq datasets creates expression quantitative trait locus (eQTL) maps for multiple ancestries and brain regions, predicts cell-type-dependent eQTLs and produces gene networks. This prioritizes genes for multiple brain-related diseases, serving as a promising step toward the identification of central nervous system (CNS) drug targets.

Using laser-capture microdissection and whole-genome sequencing of individual crypts, we characterized the landscape of somatic mutations in human small intestinal epithelium. Mutational signatures of APOBEC mutagenesis were found frequently and are probably due to the activity of APOBEC1, which is expressed at high levels in the small intestine.

Using a series of mouse mutants, we found that the Sox2 promoter does not require CTCF–cohesin loops to interact with distal enhancers. Surprisingly, mice with varying numbers of CTCF motifs in different positions showed that some distal enhancers can bypass boundaries that are created by CTCF–cohesin loops to ensure robust Sox2 expression.

Current methods of chromatin analysis focus mainly on the most abundant cell types in a sample. We present a workflow that combines enrichment of rare cell types with high-resolution mapping of histone modifications, which enables us to study chromatin dynamics in rare stem and progenitor cell populations.

Endometriosis affects around 10% of individuals born with a uterus, yet we know remarkably little about its underlying biology. Our single-cell transcriptional profiling of endometrial-type epithelial and stromal cells is shedding light on the cells and processes that contribute to endometriosis, which opens up new avenues for diagnostics and therapeutics.

A high-throughput reporter gene assay for use in living tissues has been developed. The assay allows investigators to quantify, in parallel, the activities of reporter genes in each of the cell types that constitute a tissue.

The cell types of the lung enable gas exchange and protect against infection. Our spatial atlas of the human lung and airways revealed 11 new cell types and mapped their anatomical locations. In particular, we defined the gland-associated immune niche (GAIN), which is involved in fighting respiratory infections.

It is well known that dietary composition affects lifespan, but whether the effects of diet are mediated through interactions with genetics is unknown. By careful tracking of genome-wide allele frequency in Drosophila, we identify hundreds of loci that affect longevity only in the context of a high-sugar diet.

We profiled human DNA methylation for 987 GTEx samples across nine tissues and characterized how genetic regulation of the methylome, compared with the transcriptome, contributes to GWAS phenotypes. This resource contributes to our understanding of molecular regulatory mechanisms in human tissues and their effects on complex traits.

We developed a CRISPR-based functional assay for genetic sequence variants found in human disease, probing their effects on cell proliferation, survival, motility and any physiological or pathological process measurable by fluorescence-activated cell sorting (FACS). The assay accurately assessed variant pathogenicity, drug responsiveness or resistance and mechanistic role in disease, in vitro and in vivo.

High-grade serous ovarian cancer, the most common form of the disease, is often fatal. This study investigated the genomic and immune characteristics of tumors from women who survived more than 10 years after their initial diagnosis, and compared them with short-term and moderate-term survivors.

Adult human kidney organoids or tubuloids are derived from an epithelial CD24⁺ subpopulation in the proximal nephron and can be utilized for advanced disease modeling of the most common hereditary kidney disease: autosomal dominant polycystic kidney disease.

Genome sequencing and analysis of public epigenomic data enabled the identification of disease-causing variants in a non-coding regulatory region of hexokinase 1 (HK1) in individuals with congenital hyperinsulinism. These variants caused inappropriate HK1 expression within pancreatic β-cells, which led to increased insulin secretion and hypoglycemia.

Cancer cells frequently amplify oncogenes on DNA molecules outside of chromosomes — extrachromosomal DNA. A technique adapted for isolation of extrachromosomal DNA, termed CRISPR-CATCH, enables analyses of its genetic and epigenetic compositions, which provides insights into its origin, structural diversity and mechanism of oncogene activation in cancer.

We present a high-resolution genomic variation map that greatly expands the sequence information for maize and its wild relatives in the Zea genus. Population genetics of Zea spp. provide a vast trove of adaptive alleles that are absent in maize, with the potential for accelerating future breeding by reintroducing genetic diversity.

The ability to predict gene-expression landscapes at single-cell resolution has long been a challenge in the field of genomics. We mapped whole-body single-cell transcriptomic landscapes of zebrafish, Drosophila, and earthworm using Microwell-seq. We propose the first sequence-based model, Nvwa, that can predict gene expression at single-cell resolution directly from genomic sequences.