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The culture of genetically unmodified human naive embryonic stem cells in specific growth conditions gives rise to structures that recapitulate those of post-implantation human embryos up to 13–14 days after fertilization.

In mice, a SPOCD1–TPR-dependent ‘nowhere-to-hide’ mechanism is required for complete non-stochastic piRNA-directed LINE1 DNA methylation by preventing transposons from escaping surveillance within heterochromatin.

The authors show that babies conceived during the COVID-19 pandemic have a different parental socioeconomic composition than expected had the pandemic not occurred.

The genomes of 28 ancient southern African individuals dated to between 10,200 and 150 years before present offer insights into the evolution of Homo sapiens.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

In B-cells, super-silencers originally help activate important genes during early development. Later, they switch roles and become powerful silencers in mature B cells. Super-silencers help control gene activity in healthy B-cells, but when they malfunction or mutate, they may drive the development of B-cell cancers. In healthy, mature B cells, super-silencers keep developmental genes switched off to maintain cell identity. When disrupted by mutation or malfunction, these elements can reverse their role and contribute to the development of B-cell cancers.

Here the authors perform a genome wide association study of 204,747 Estonian Biobank participants revealing 214 BMI loci. Reported signals include ADGRL3, PTPRT, and a protein-truncating POMC variant with strong BMI effects, implicating leptin-melanocortin pathways and highlighting targets for obesity intervention.

Combining microscopy and modeling, the authors reveal that tissue fluidity, driven by active cell motion and interfacial tension, governs how living spheroids merge into larger structures.

Co-ChIP, a method for measuring the genome-wide co-occurrence of histone marks, sheds light on the complexity of the histone code.

Gliomas are tumors often associated with epigenetics-related gene deregulation. Here the authors reveal an atlas of active enhancers and promoters in benign and malignant gliomas by performing whole-genome mapping of chromatin accessibility, histone modifications, DNA methylation patterns and transcriptome analysis simultaneously in multiple tumor samples.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

Elevated expression of long noncoding RNA H19 is seen in clinical samples of neuroendocrine prostate cancer (PCa). Here the authors show H19 promotes plasticity from luminal to neuroendocrine by epigenetic reprogramming.

The H3K27 demethylase Utx is reported to be a critical regulator for the initiation of somatic and germ cell reprogramming.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

This study shows that the combination of naive pluripotency growth conditions, Oct4, Sox2, Klf4 and Myc (OSKM) overexpression, and depleting the Mbd3/NuRD co-repressor results in deterministic and synchronized reprogramming to pluripotency.

Tan et al. identify PRDM16 as a key repressor of fibrotic switching in smooth muscle cells and show that its downregulation in atherosclerosis drives smooth muscle cells toward a synthetic fate, promoting fibrous plaques.

Magnetic reconnection, thought to drive solar eruptions, has been studied with remote sensing. The Parker Solar Probe has directly measured reconnection-associated plasma properties in situ in the solar corona, deepening our understanding of the process.

It is known that human embryonic stem (ES) cells are more similar to mouse primed epiblast stem cells than to naive mouse ES cells; here culture conditions are determined that allow human ES and induced pluripotent stem cells to acquire a pluripotent state that retains growth characteristics highly similar to mouse naive ES cells, and competence in generating cross-species human-mouse embryonic chimaerism.

MLLT3 is identified as a crucial regulator of the self-renewal of human haematopoietic stem cells, and helps to maintain an active chromatin state in haematopoietic stem-cell regulatory genes during culture.

The Dog Genome Annotation (DoGA) study is based on 5’ transcriptomics of 132 dog tissues. Here the authors identify over 100,000 promoters and provide an expression atlas to facilitate regulatory understanding of disease, morphology and behavior.

Characterizing the cellular stages that lead to induced reprogramming is of much interest and cell surface markers could offer unique advantages for this. Here the authors use surface proteomics and discover CD24 as a marker that tracks reprogramming-responsive cells and enables the analysis and enrichment of transgene-dependent and -independent induced pluriopotent stem cells.

The SWI/SNF chromatin remodeling complex is frequently mutated in cancer and neurodevelopmental disorders. Here, the authors performed a CRISPR screen and identified MLF2 and RBM15 as modulators of SWI/SNF assembly, revealing new therapeutic targets for diseases caused by impaired chromatin remodeling.

PWWP domains of DNMT3A and DNMT3B are proposed to interact with H3K36me3. Here the authors present a mouse model carrying a D329A point mutation in the DNMT3A PWWP domain and find this causes dominant postnatal growth retardation, with aberrant progressive gain of DNA methylation across domains marked by H3K27me3 in adult tissues.

The mechanism by which ingested material accesses the cytosol for cross-presentation is unclear. Caetano Reis e Sousa and colleagues demonstrate that signaling via the lectin receptor DNGR-1 ruptures the phagosome and releases its contents to the cytosol for cross-presentation.

The canonical metal-organic framework ZIF-8 does not melt and form a glass. Here, authors incorporated two additional organic linkers into ZIF-8 to generate meltable derivatives which can be transformed into highly porous glasses by melt-quenching.

MEF2C is a transcription factor required for B-cell proliferation. Here the authors show that MEF2C is also needed in B-cell development and recovery from stress by inducing expression of DNA repair factors that prevent double stranded breaks and enable VDJ recombination.

Guetter et al. identify a melanoma-associated chondroitin sulfate proteoglycan-positive subpopulation of metastasis founder cells from lymph node biopsies of patients with melanoma and observe that they mediate immune evasion and predict systemic metastasis and poor outcomes.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Genome-wide analyses identify 30 independent loci associated with obsessive–compulsive disorder, highlighting genetic overlap with other psychiatric disorders and implicating putative effector genes and cell types contributing to its etiology.

Pluripotent stem cells can be generated in the laboratory through somatic cell nuclear transfer (generating nuclear transfer embryonic stem cells, ntESCs) or transcription-factor-based reprogramming (producing induced pluripotent stem cells, iPSCs). These methods reset the methylation signature of the genome — but to what extent? Here it is found that mouse iPSCs 'remember' the methylation status of their tissue of origin, but the methylation of ntESCs is more similar to that of naturally produced ES cells.

Temporally dynamic extraembryonic and embryonic BMP4 signalling shapes mouse embryo lineage choices.

Electrical stimulation of the neuromuscular system holds promise for therapeutic biomedical applications, but is currently restricted by power. Here, the authors introduce fully implantable resonator-based designs achieving ±20 V compliance and >300 mW output, enabling multichannel, biphasic, current-controlled operation to evoke functional gate patterns for 6-weeks in freely behaving rats.

While EGFR tyrosine kinase inhibitors (TKIs) are often effective in EGFR mutant lung cancer, resistance often occurs. Here, the authors identify intratumoural heterogeneity of EGFR expression and find that EGFR-low cells are more tolerant to EGFR-TKI, promoting resistance.

Leukemias with ambiguous lineage require further characterisation. Here, the authors perform epigenomic and transcriptomic analysis of a subgroup of such leukemias with CpG Island Methylator Phenotype and propose that epigenetic dysregulation and not genetic lesions explains their mixed phenotype.

During oogenesis, H3K4 trimethylation is targeted to genomic elements through transcription-dependent and transcription-independent mechanisms, the latter relying on MLL2 recruitment to unmethylated CpG-rich regions.

Intracortical recordings in humans reveal that auditory stimulation during sleep induces robust spiking and high-gamma responses, whereas alpha–beta desynchronization—likely reflecting neural feedback processes—is reduced compared to wakefulness.

The Huntington's disease (HD) induced pluripotent stem cell (iPSC) consortium describe the combined use of differentiated patient-derived iPSCs and systems biology to discover underlying mechanisms in HD. They identify neurodevelopmental deficits in HD cells that can be corrected in cells and in vivo with a small molecule.

Basal cells, rather than neuroendocrine cells, have been identified as the probable origin of small cell lung cancer and other neuroendocrine–tuft cancers, explaining neuroendocrine–tuft heterogeneity and offering new perspectives for targeting lineage plasticity.

Genetic, ecological and simulation data demonstrate that the origin and coexistence of reproductively isolated sympatric groups in a fungus is driven by pleiotropic vegetative incompatibility genes under balancing selection.

G protein-coupled receptors (GPCRs) are expressed in different cell types of the brain. Their joint network function remains unclear due to lack of molecular tools allowing functional dissection targeting a single type of GPCR. Here the authors use optogenetics and show how serotonergic 5-HT2A receptors act across excitatory and inhibitory neurons in mouse visual cortex.

During mammalian embryogenesis, extraembryonic tissues are required for the patterning and morphogenesis of the embryo. This Review discusses how signalling networks and epigenetic modifications regulate the development and function of the different extraembryonic tissues during implantation, axis specification and gastrulation.

Single-cell mapping of chromatin accessibility, DNA methylation and RNA expression during gastrulation in mouse embryos shows characteristic epigenetic changes that accompany formation of the primary germ layers.

ZNF524 is a newly described protein that binds to telomeres, the ends of linear chromosomes. ZNF524 promotes the presence of two members of the shelterin complex, TRF2/RAP1, at telomeres, and prevents genomic instability.

Recent advances in our understating of the molecular underpinnings of alternative primed- and naive-like pluripotent states in rodents and humans highlight potential functional benefits of naive pluripotency and identify key unanswered questions in this rapidly evolving field.

Human embryonic stem cells are differentiated to cells similar to the embryonic aorta-gonad-mesonephros, which gives rise to hematopoietic stem cells.

A data-analytical approach that can extract the history and dynamics of complex systems from noisy snapshots on timescales much shorter than the uncertainty with which the data were recorded is described; the approach is demonstrated by extracting the dynamics on the few-femtosecond timescale from experimental data recorded with 300-femtosecond timing uncertainty.

Precise protease positioning and gating of the proteasome core require the ordered assembly of 28 subunits. Cryo-EM structures of seven intermediates visualize five dedicated chaperones and three propeptides mediating step-by-step assembly of the human 20S proteasome.