Research Briefing

We construct a chromosome-level genome assembly of the acorn barnacle Amphibalanus amphitrite. Using this genome together with multi-omics datasets and functional evidence, we reveal the evolution and function of two lineage-specific genes, bcs-6 and bsf, that help A. amphitrite adapt to a sessile lifestyle.

This study establishes in vitro and in vivo systems to study mutagenesis and cancer genome evolution. Using microfluidics and mouse models, the method enables the dissection of co-occurring mutational processes and reveals that acute damage results in mirror-image mutation phasing between sister cells after a single mitosis.

Chromosome-level genome sequences of 69 diverse Arabidopsis thaliana strains reveal a quasi-fixed genome structure worldwide, in which large rearrangement is limited almost exclusively to the centromeric regions. Pan-genome analysis uncovered substantial diversity in gene content that, together with the genome assemblies, will fuel future genetic research.

Using single-cell RNA-sequencing (scRNA-seq) of lung tissue, expression quantitative trait loci (eQTLs) were mapped across 38 cell types, revealing both shared and cell-type-specific effects. Highly cell-type-specific disease-interaction eQTLs were linked to cellular dysregulation in lung disease and lung disease risk variants were connected to their regulatory targets in relevant cell types.

We have curated a comprehensive single-cell reference map of the human breast. Our data explore how age, parity and germline mutations might influence cellular dynamics, revealing unexpected signs of immune exhaustion in healthy tissues from carriers of BRCA1 or BRCA2 germline mutations.

In mice, zygotic genome activation occurs at onset of the two-cell stage in embryonic development and coincides with the exit from totipotency. Our work shows that the transcription factor DUXBL participates in silencing part of the stage-specific two-cell-associated transcriptional program and is required for development to proceed.

We show that in addition to promoter activation, MYC drives cancer progression by activating transcriptional enhancers via a distinct mechanism. MYC cooperates with several other proteins at these cis-regulatory regions to change the epigenome and promote recruitment of RNA polymerase II and enhancer transcription.

Genome-wide CRISPR screening coupled with ATAC-see uncovered modulators that influence global chromatin accessibility. Notably, TFDP1 emerged as a pivotal modulator of chromatin accessibility that acts by controlling histone transcription. Depletion of TFDP1 induced a global elevation in accessibility, enhancing the efficiency of genome editing and iPS cell reprogramming.

We constructed a pan-genome using 27 high-quality representative Brassica oleracea genomes. Using this pan-genome, together with multi-omics datasets from large-scale populations, we uncovered the important role of structural variations as dosage regulators of gene expression, which drives the morphotype diversification in B. oleracea.

Skin color is highly variable in Africans, but the underlying molecular mechanisms remain poorly understood. Using population genetics and functional genomics, we identified key genetic variants, regulatory elements and genes that affect skin pigmentation, an adaptive trait, which provides valuable insights into the mechanisms underlying human skin color diversity and evolution.

The genetic background of pediatric acute myeloid leukemia (AML) does not fit with classification systems developed for adult AML. This study investigates the genetic background of pediatric AML and proposes a genomic framework for improved classification and risk stratification based on the driver alterations.

Polymorphisms in the non-coding genome affect genetic circuits and result in variable immune responses across individuals. Here we report a genetic circuit involving a long non-coding RNA (lncRNA) that spatially coordinates chromatin contacts to control pro- and anti-inflammatory gene expression and shape immune responses of healthy individuals to pathogens or vaccination.

EasySci, a scalable single-cell profiling technique, uncovered over 300 mammalian brain cell states, revealing molecular features and dynamics of rare cell states linked to aging and Alzheimer’s disease. This work offers insights into cell states that expand (rare astrocytes and vascular leptomeningeal cells in the olfactory bulb, reactive microglia, and oligodendrocytes) or are depleted (neuronal progenitors, neuroblasts and committed oligodendrocyte precursors) during normal and pathological aging.

Combined analysis of genome-wide association studies and epigenetic data has identified certain immune cell types as drivers of autoimmune disease, but current methods have not been able to pinpoint key effector immune cell states. Using single-cell data from inflammatory tissues, we identified effector cell states embedded within inflammatory tissues — including T peripheral helper cells and tissue regulatory T cells — that capture disproportionate disease heritability.

We present a model to predict the chance of each possible de novo mutation in the human genome informed by recent insights into determinants of mutagenesis. Predictions were applied to refine demographic models, identify constrained genes, and uncover mutagenic effects of polymerase III transcription and transcription factor binding in testis.

Whole-genome sequencing data of individuals from the UK Biobank and Iceland and a somatic mutation barcoding strategy enabled detection of clonal hematopoiesis at scale. This comprehensive study provides insights into the epidemiology, somatic and germline genetics, and disease associations of clonal hematopoiesis.

Previous studies reported an effect of N⁶-methyladenosine (m⁶A) of super-enhancer RNAs (seRNAs) on chromatin accessibility and gene transcription. We investigated seRNA m⁶A levels in pancreatic ductal adenocarcinoma (PDAC) and found that aberrantly increased m⁶A methylation promoted local chromatin accessibility, resulting in increased transcription of oncogenes acting in PDAC progression.

We present an analysis that shows that although nearly half of the human genome comprises repetitive sequences, recombination between homologous repeats has a minor role in cancer chromosomal evolution.

Whole-exome and genome sequencing in consanguineous families with unsolved lipodystrophy identified biallelic pathogenic loss-of-function variants in the phospholipase gene PLAAT3. Multi-omics and functional analyses in human and mouse PLAAT3-deficient adipose tissue and adipose stem cells revealed an adipocyte differentiation defect that is mediated by an altered gene network downstream of the adipogenesis master regulator PPARγ.

We developed a computational, age-dependent topic model to identify longitudinal comorbidity patterns from hospital diagnosis data. The inferred comorbidity patterns are robust across UK and US populations and identify disease subtypes with distinct genetic profiles.