Volume 54 Issue 8, August 2022

A new study uses single-cell and spatial transcriptomics to provide a systematic characterization of the recurrent gene-expression programs that control neoplastic cell states in diverse cancers.

The impact of endogenous retrovirus silencing during mammalian development is poorly understood. A new study shows that their abnormal reactivation in pluripotent cells dismantles key gene regulatory networks by perturbing transcriptional condensates linked to super-enhancer function.

Systematic CRISPR screens in primary human T cells uncovered the upstream regulators of crucial immune genes — IL2RA, IL2 and CTLA4. Then, using RNA-seq and ATAC-seq in knockout T cells, we mapped the downstream target genes and non-coding cis-regulatory elements of key regulators, thereby revealing a regulatory network enriched for immune disease-associated genes.

Genetic and phenotypic analyses of data from over 400,000 participants in the UK Biobank identified 10 new loci associated with the development of clonal hematopoiesis and implicated DNA damage, oncogene signaling, telomere maintenance and blood cell homing in its pathogenesis. These findings can help to decipher the pathogenesis of clonal hematopoiesis and develop therapeutic approaches.

Assemblies of hexaploid cultivated oat, and of close relatives of its diploid and tetraploid progenitors, have revealed its polyploid formation and subgenome evolution. These high-quality oat reference genomes will facilitate the discovery of candidate genes that underlie beneficial traits such as hulless grain and disease resistance.

In the zebrafish heart, several transient fibroblast types appear after injury. High-throughput lineage tracing revealed that injury-responsive fibroblasts are derived from two distinct lineage origins: the epicardium and the endocardium. Targeted cell-type-specific depletion showed that at least one fibroblast type has a critical role in heart regeneration.

Genome-wide CRISPR knockout and activation screens in human lung epithelial cells with endogenous expression of the SARS-CoV-2 entry factors ACE2 and TMPRSS2 identify mucins as key host factors restricting viral infection.

Genome-wide CRISPR knockout and activation screens in Calu-3 lung cells and Caco-2 colorectal cells identify host factors regulating SARS-CoV-2, MERS-CoV and seasonal HCoVs.

Genetic and functional studies implicate allele-specific regulation of OAS1 splicing and nonsense-mediated decay in COVID-19 severity. The OAS1 risk haplotype is also associated with reduced SARS-CoV-2 clearance in a clinical trial with pegIFN-λ1.

Analyses of the polygenic architecture of childhood, persistent and late-diagnosed attention-deficit hyperactivity disorder (ADHD) in a Danish population-based case–cohort sample identify differences among ADHD subgroups with respect to common and rare variants.

Genome-wide association meta-analysis of insomnia in 593,724 cases and 1,771,286 controls identifies 554 risk loci and implicates specific biological pathways through gene prioritization.

Pooled loss-of-function CRISPR screens in primary human T cells identify upstream regulators of IL2RA, IL-2 and CTLA4. Individual knockouts of 24 regulators of IL2RA define a central network enriched for genes associated with immune-mediated diseases.

Transcriptomic and epigenomic profiling of human microglia identifies putative gene regulatory mechanisms for 21 Alzheimer’s disease (AD) risk loci. SPI1/PU.1 is nominated as a key regulator of microglia gene expression and AD risk.

Analysis of whole-exome sequencing data from 200,453 UK Biobank participants identifies loci associated with clonal hematopoiesis and highlights causal links between clonal hematopoiesis and other traits.

A cross-ancestry genome-wide association meta-analysis of lung cancer including 61,047 cases and 947,237 controls identifies five new cross-ancestry susceptibility loci and highlights ancestry-specific effects of common and rare variants on lung cancer risk.

Single-nucleus and spatial, whole-transcriptome profiling of 43 pancreatic adenocarcinomas provides a refined molecular and cellular classification, highlighting a new neoadjuvant treatment-associated neural-like progenitor tumor cell state.

Pan-cancer single-cell and spatial transcriptomic profiling identifies recurrent gene modules that underlie a continuum of cancer cell states. Tumor microenvironment influences the occurrence of these states.

YAP upregulates TET1, which physically interacts with TEAD1/4 to demethylate DNA at YAP target genes in the liver. Loss of TET1 reverses YAP-induced chromatin and transcriptional changes and suppresses YAP-induced hepatomegaly and tumorigenesis.

Biallelic loss-of-function variants in FOCAD cause a syndromic form of pediatric liver disease by compromising the SKI messenger RNA surveillance pathway.

Single-cell RNA sequencing and spatiotemporal analysis of the regenerating zebrafish heart identify transient proregenerative fibroblast-like cells that are derived from the epicardium and the endocardium. Wnt signalling regulates the endocardial fibroblast response.

TRIM28 depletion in embryonic stem cells disconnects transcriptional condensates from super-enhancers, which is rescued by knockdown of endogenous retroviruses.

A reference-quality genome assembly of hexaploid oat variety ‘Sanfensan’ and genome assemblies of its diploid and tetraploid Avena ancestors provide insights into the evolutionary history of allohexaploid oat.