Research Briefing in 2024

An analysis of somatic mutations in blood exomes from 200,618 individuals revealed previously unrecognized genes driving clonal hematopoiesis. Mutations in these genes showed age-dependent clonal expansion and their presence correlated with heightened risks of infection, death and hematological malignancy.

We adapted Tn5 transposition to reduce the amount of input DNA required for amplification-free single-molecule real-time Pacific Biosciences sequencing. We applied transposition-based library preparation in two sensitive methods for concurrently resolving genomes and epigenomes using limiting amounts of native DNA.

Many plant products eaten daily in human diets — such as potato or banana — are polyploid and are notoriously difficult to breed. In this study, the fusion of clonal gametes from distinct diploid tomato parents is used as a blueprint for the design of polyploid genomes in crops.

By developing a modular system for precision epigenome editing, we were able to delineate the causal and quantitative role of chromatin modifications in transcription regulation. The precise effect of chromatin modifications is influenced by multiple contextual factors, including the underlying DNA sequence, transcription factor occupancy and genomic positioning.

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.