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Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

Here, Libertini and colleagues devise a computation tool that can analyze whole-genome bisulfite sequencing (WGBS) data to recover of ∼30% of the lost differential methylation position information. They use COMETgazer and COMETvintage to analyze 13 diffferent methylome data to demonstrate their performance.

This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the molecular basis of human disease.

The mechanisms underlying neuron specification and maturation are unclear. Here the authors provide an integrated epigenomic and transcriptomic analysis of mouse and marmoset neocortical neuronal classes. Pan-neuronal programs active during early development are more evolutionary conserved but not neuron-specific, whereas pan-neuronal programs active during later stages of maturation are more neuron- and species-specific.

Single-cell profiling in the human cortex reveals aging-associated transcriptomic changes across all brain cell types, which overlap with effects with Alzheimer’s disease and show a convergent signature with psychopathology across multiple cell types.

Chemical experiments on californium are stymied by isotope availability and radioactivity considerations, but are advanced here with synthesis and characterization of an organometallic complex.

Here, the authors reveal using single-cell RNA sequencing that Parkinson’s disease (PD) patient-derived neuronal cells show altered primary cilia morphology and signaling suggesting cilia dysfunction may underlie PD pathogenesis.

Results show the minimum sequencing depth required for the discovery of differentially methylated regions at desired sensitivity and specificity and the trade-off between adding more replicates versus increasing sequencing depth.

Induced neurons, but not induced pluripotent stem cell (iPSC)-derived neurons, preserve age-related traits. Here, the authors demonstrate that blood-derived induced neural stem cells (iNSCs), despite lacking a pluripotency transit, lose age-related signatures.

Whole-genome bisulphite sequencing data from diverse human cell and tissue types shows that only about 22% of CpGs change their methylation state across these cell types; most of these CpGs are located at gene regulatory elements, particularly enhancers and transcription-factor-binding sites, and these selected regions with dynamic DNA methylation patterns could help to define putative regulatory elements further.

Manipulating the topological phases of quantum materials is necessary to fully leverage their potential for future electronics. Here, the authors experimentally demonstrate the controllable transition from a weak to a strong topological insulator phase through the in-situ application of high strain.

The addition of a Notch signaling inhibitor to both mouse and human keratinocytes bypasses the use of oncogenes and p53 to increase transcription factor mediated–pluripotent stem cell reprogramming through blocking p21 expression.

Profiling pluripotent stem cell (PSC)-derived neural progeny is of fundamental interest for characterizing stem cell differentiation. Here, the authors analyse neural progenitors consecutively derived from human PSCs, showing dynamic stage-specific transcriptional patterns for distinct neural progenitors.

Alexander Meissner and colleagues use CRISPR/Cas9 genome editing to inactivate the DNA methyltransferases DNMT1, DNMT3A and DNMT3B in human embryonic stem cells (ESCs). They find an essential role for DNMT1 in human ESCs and generate genome-wide maps of the DNA methylation changes that occur following inactivation of these enzymes.

Investigation of FOXA2, GATA4 and OCT4 binding across several cell types provides insights into the genetic determinants and epigenetic effects of pioneer-factor occupancy. The data suggest that FOXA2 samples most of its potential binding sites but is stabilized at only a subset of targets.

A lag in nascent strand DNA methylation contributes to heterogeneous methylation in asynchronous cell populations, but cancer cells and active transcription factor binding sites preserve heterogeneity even after cell cycle arrest.

Catalytically inactive Cas9 fused to a methyltransferase has emerged as a promising epigenome modifying tool. Here the authors generate a methylation depleted but maintenance competent mouse ES cell line and find ubiquitous off-target activity.

The integrative analysis of epigenetic footprints along consecutive stages of neural progenitors derived from human ES cells reveals regulatory mechanisms that orchestrate stage-specific differentiation.

Lineage-specific transcription factors and signalling pathways cooperate with pluripotency regulators to control the transcriptional networks that drive cell specification and exit from an embryonic stem cell state; here, we report genome-wide binding data for 38 transcription factors combined with analysis of epigenomic and gene expression data during the differentiation of human embryonic stem cells into the three germ layers.

The competition between the formation of different phases and their kinetics need to be clearly understood to make materials with on-demand and multifaceted properties. Here, the authors reveal, by a combination of complementary in situ techniques, the mechanism of a Cu-Zr-Al metallic glass’s high propensity for metastable phase formation, which is partially through a kinetic mechanism of Al partitioning.

This Perspective highlights the global consensus on the urgency and growing threat of invasive alien species, and management needs, as found by the 2023 report on invasive alien species conducted by the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES).

Giulitti et al. deliver modified mRNAs encoding OCT3/4, SOX2, KLF4 and cMYC as well as NANOG in microfluidics to directly convert human fibroblasts into naive induced pluripotent stem cells; the confined environment leads to enhanced efficiency and homogeneity compared to traditional methods.

With widespread generation and availability of synthetic data, AI systems are increasingly trained on their own outputs, leading to various technical and ethical challenges. The authors analyse this development and discuss measures to mitigate the potential adverse effects of ‘AI eating itself’.