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Multiomic analysis of blast-phase myeloproliferative neoplasms identifies a chromosome 21 amplicon harboring DYRK1A as a clonal and therapeutically targetable event in around a quarter of cases.

Tissue-resident macrophages (TRM) are important mediators of local immunity. Here the authors show that the deficiency or inhibition of a kinase, WNK1, unlinks macrophage colony-stimulating factor signaling and resulted macropinocytosis with the downstream, potentially IRF8-mediated genetic program to bias progenitor differentiation to neutrophil instead of TRM.

Species synchrony is considered a major mechanism of biodiversity–ecosystem stability relationships. Here, by combining theory, modelling and empirical work, the authors show that with time series length species synchrony decreases and its relationship with diversity switches from positive to negative.

Immune checkpoint blockade activates T cell immunity by reprogramming the STAT3 and STAT5 transcriptional pathways in dendritic cells, and STAT3 degradation is effective for treating tumours of multiple cancer types in mouse models.

Whether multimorbidity accelerates brain Aβ deposition in humans remains largely unknown. Here, the authors demonstrate that higher self-reported multimorbidity burden predicts increased brain Aβ accumulation rates in the ADNI cohort.

The role of vascular plasticity in brain function remains poorly understood. Here, the authors demonstrate that a significant portion of blood vessels in the adult brain periodically occlude and regress, a process that is associated with a reduction in neuronal activity.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Whether the adult testis harbours a somatic progenitor population is unknown. Here, the authors provide evidence that the testis interstitial cells expressing the transcription factor Tcf21 maintain adult testis homeostasis during aging, and act as potential reserve somatic progenitors following injury.

In this Review the authors explain how different routes of exposure to food antigens can contribute to the development of food allergies. They discuss how allergic sensitization occurs against food antigens and focus on how IgE and mast cells ultimately drive the allergic pathology.

A comprehensive analysis of the cell-specific molecular regulatory mechanisms underlying post-traumatic stress disorder in the human prefrontal cortex.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

The validation of inhibitors targeting PurF, a novel drug target for tuberculosis drug discovery, is described.

The Somatic Mosaicism across Human Tissues Network aims to create a reference catalogue of somatic mosaicism across different tissues and cells within individuals.

Gene isoforms are quantified with a machine learning method that optimally integrates long and short sequencing reads.

A combination of metagenomic data from experimental and natural warming with microbial culturing experiments shows that warming increases the potential of evolution of antibiotic resistance in soil bacteria.

Exposure of mice to high fructose during gestation or early postnatal life causes decreased microglial phagocytosis during brain development and leads to anxiety-like behaviour in adolescence.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Using a genome-wide CRISPR knock-out screen, the authors defined the repertoire of genes that are required for proerythroblast survival and for terminal erythroid differentiation.

Fish retinal regeneration starts with the dedifferentiation of glia cells into progenitors. Following injury, the proneural transcription factor, Ascl1a, upregulates the pluripotency factor Lin-28, which in turn prevents let-7 microRNA-mediated inhibition of regeneration-associated genes.

Here, the authors leverage whole-genome sequencing from >88,000 diverse individuals to uncover 18 BMI-related genetic signals, including novel variants in participants of African genetic ancestry, highlighting the value of diversity in genetic discovery.

HIV infection has been difficult to cure because of uncharacterized reservoirs of infected cells that are resistant to antiretroviral therapy. This study shows that some hematopoietic stem cells are latently infected and may therefore constitute such a reservoir.

A study of human and mouse models of pancreatic cancer finds that inhibiting the lipid kinase PIKfyve interferes with the cancer’s lipid homeostasis, making it a potential target for drug development.

Protein structures are predicted by integrating deep learning potentials with iterative threading fragment assembly simulations.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Wastewater treatment plants are important reservoirs of antibiotic resistance genes (ARGs). Here, the authors analyze ARGs in a global collection of samples from wastewater treatment plants across six continents, providing insights into biotic and abiotic mechanisms that appear to control ARG diversity and distribution.

Genomic studies often lack representation from diverse populations, limiting equitable insights. Here, the authors show that the BIG Initiative captures extensive genetic diversity and reveals ancestry-linked health disparities in a community-based Mid-South cohort.

The tumour suppressor PTEN is required for maintenance of haematopoietic stem cells, but not leukaemia-initiating cells — this specific effect is mediated by the mTOR pathway and mitigated by rapamycin.

Systematic analysis from the Global Burden of Disease study reported that, despite global improvements from 1990 to 2021, dietary iron deficiency-associated disease burden remains high in women, children and residents in low socio-demographic index countries.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Memristors hold promise for massively-parallel computing at low power. Aguirre et al. provide a comprehensive protocol of the materials and methods for designing memristive artificial neural networks with the detailed working principles of each building block and the tools for performance evaluation.

The molecular mechanisms that drive hematopoietic stem cell functional decline under conditions of telomere shortening are not completely understood. Here the authors demonstrate that hematopoietic stem cells with short telomeres induced by mutations affecting telomerase complex genes undergo differentiation towards megakaryopoiesis through the activation of the IFI16-mediated interferon response.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

The calvarial stem cell niche is populated by a cathepsin K-expressing cell lineage and a newly identified discoidin ___domain-containing receptor 2-expressing lineage, both of which are required for proper calvarial mineralization.

In this Review, the authors present a roadmap towards achieving consensus on development, analysis and interpretation of single-cell transcriptomics data in adipose tissue, including discussion of roadblocks, best practices and ideal cell-type markers for annotation of adipose tissue cell types in mice and humans.

Subsets of ILC3s upregulate the immunoregulatory checkpoint molecule CTLA-4 after stimulation in a microbiota-dependent manner, and advances to support CTLA-4⁺ ILC3s may represent a treatment opportunity in IL-23-driven chronic inflammation.

The freshwater planarian S. mediterranea is an important model organism for regeneration research but its use in aging research is little explored and S. mediterranea is commonly referred to as immortal. Here Dai et al. report age-associated physiological and molecular changes in the sexual lineage of S. mediterranea, and global reversal of such changes after regeneration.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

Multipotent progenitor cells are like stem cells in their ability to form many kinds of differentiated cells, but they are not able to self renew and thus have a limited lifespan. This paper reports that by mutating only three genes, it is possible to convert multipotent progenitor cells into long-term renewing cells. It is shown that these three genes normally prevent progenitors from self renewing, and suggest a mechanism by which mutations in progenitor cells could cause cancer.