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Elucidating the nature of the metallocofactors in nitrogenase enzymes, and preparing synthetic analogues of these clusters, is a classic target for bioinorganic chemists. Now the transformation of [Fe₂S₂]²⁺ rhombs to [Fe₈S₈]ⁿ⁺ clusters has been achieved through a series of redox- and ligand-substitution reactions.

The ability to visualise stochastic invasion events is limited in murine models of metastatic cancers. Here the authors use a transparent zebrafish epidermis model to follow the invasion events of K-Ras transformed epithelial cells and show that these cells invade through basal cell extrusion.

Mutations in linker 2 of KLF1 are identified in cases of non-spherocytic hemolytic anemia. Here, the authors show the molecular mechanisms of disease due to linker 2 mutation in mice using ChIPseq and RNAseq.

In this work, Yoshinaga et al. use functional CRISPR screens and in vivo analyses to show that an RNA methyltransferase METTL16 and MTR4-nuclear exosome play an essential role in maintaining erythropoiesis and regulating DNA repair in erythroblasts.

Human TNF is required for respiratory-burst-dependent immunity to Mycobacterium tuberculosis in macrophages but seems to be largely redundant physiologically.

Ionizing radiation damages the gastrointestinal system, but the cell types involved in intestinal damage and repair are controversial. Here the authors use bone marrow transplantation models and various irradiation regimes to rule out a role of bone marrow-derived cells in acute gastrointestinal injury and recovery in mice.

SRPK1, a kinase involved in splicing regulation, is a potential therapeutic target for AML patients. Here, the authors show that SRPK1 inhibition changes isoform levels of key epigenetic regulators, including BRD4, and it has anti-tumor effects specifically against MLL-rearranged AML cells.

Mast cells within the tumor microenvironment have controversial roles. Here, the authors show, using genetic mouse models, that in gastric cancer, mast cells at the periphery of the tumors are activated via cancer cell produced-IL33 and promote tumorigenesis by recruiting macrophages within the tumors.

Michael Dussiot et al. show that an activin receptor IIA ligand trap ameliorates anemia in a mouse model of β-thalassemia by blocking the deleterious effects of GDF11. Mechanistically, GDF11 inactivation reversed ineffective erythropoiesis by promoting terminal erythroblast differentiation and by inducing apoptosis of immature erythroblasts. Also in this issue, Rajasekhar Suragani et al. show related findings using a modified activin receptor IIB ligand trap.

Salmonella infection is a common complication in people with malaria. Here the authors show that induction of heme oxygenase-1, a mechanism of tolerance to malaria, impairs resistance to Salmonella infection by limiting production of bactericidal reactive oxygen species.

Primary lymphoedema can lead to the swelling of the extremities and facial dysmorphism. Here the authors present evidence that compound heterozygous and homozygous mutations inPIEZO1result in an autosomal recessive form of generalised lymphatic dysplasia.

The identity and lineage potential of the embryonic thymus-seeding progenitors that first seed the embryonic thymic rudiment is unclear. Jacobsen and colleagues find that these cells do not include multipotent stem cells or T cell–restricted progenitors but instead are lympho-myeloid progenitors.

Leukaemic stem cells in acute myeloid leukaemia are defined by a lack of expression of NKG2D ligands, which mediates their ability to evade surveillance by NK cells.

Keyl et al. present an explainable artificial intelligence model-based real-world data analysis from over 15,000 patients across 38 cancer types, identified key prognostic marker interactions, and confirmed these in an external lung cancer cohort.

CRISPR/Cas gene drives can bias transgene inheritance through different mechanisms. Here the authors use gene linkage to show that in males inheritance bias of wGDe did not occur by homing, rather through increased propagation of the donor drive element.

Chronic obstructive pulmonary disease is a severe inflammatory lung disease characterized by obstructed airflow from the lungs. Here, Seimetz et al. show that NADPH oxidase subunit 1 (NOXO1) is responsible for peroxynitrite formation from nitric oxide and superoxide and drives the development of smoke-induced emphysema and pulmonary hypertension.

Hematopoietic stem cells (HSCs) replenish blood cells. Here, Luis et al., identify a feedback mechanism by which IL-1 secreted by activated platelets signals through niche Lepr+ cells to activate HSCs and restore platelet homeostasis.

This Resource presents an atlas classifying the age-related changes in human hematopoietic stem and progenitor cells from gestation through aging.

Niche crosstalk with Haematopoietic cells underlies normal haematopoiesis and myeloid disorders. Here the authors report a Stabilin2-Cre driver mouse with Cre-activity restricted to bone marrow sinusoidal endothelial cells, and that Stabilin2-Cre driven overactivation of b-catenin leads to erythroid differentiation defects and anaemia.

Drivers of physiological aging are also linked to the etiology of chronic obstructive pulmonary disease (COPD), including inflammation and senescence, both influenced by nicotinamide adenine dinucleotide (NAD⁺) metabolism. Norheim et al. performed a randomized controlled trial in patients with COPD, testing whether boosting NAD⁺ levels reduces airway inflammation.

Transcriptomic and metabolic profiling reveals that the creatine kinase pathway is essential for growth of acute myeloid leukemias expressing the transcription factor EVI1.

Germline mutations in the DNMT3A gene can cause an overgrowth syndrome associated with behavioural and hematopoietic phenotypes. Here the authors describe a mouse model of this syndrome that recapitulates many of these features, including conserved alterations in DNA methylation in the blood cells of both species.

Differentiation therapy induces the maturation and clearance of acute myeloid leukemia cells. Here, using a mouse model, the authors show that a specific lineage of mature leukemia-derived cells persists during remission and is responsible for disease relapse.

In human β-thalassaemiaerythroblasts, HSP70 is sequestered in the cytoplasm by the excess of free α-globin chains and can no longer protect the master transcriptional factor of erythropoiesis GATA-1 from caspase-3 cleavage; transduction of a nuclear-targeted HSP70 or a caspase-3 uncleavable GATA-1 mutant restored maturation of erythropoiesis.

Using single-cell transcriptome profiling of pre-granulocyte-macrophage progenitor cells, Nerlov and colleagues identify an early hematopoietic lineage bifurcation that segregates mast cells, eosinophils, megakaryocytes and erythroid cells from monocytes, neutrophils and lymphocytes.

The commitment stage at which progenitors seed the thymus remains unclear. Jacobsen and colleagues show that the earliest progenitors in the neonatal thymus have combined myeloid, T lymphocyte and B lymphocyte potential but not megakaryocyte-erythroid potential.

Dehydrated hereditary stomatocytosis is a genetic condition in which the permeability of red blood cells to cations in increased. Albuisson and colleagues find that mutations in the mechanically-activated PIEZO1 ion channel are the major cause of the disease and result in more slowly inactivating currents.

Chromatin accessibility is a key mediator of gene expression and mutations in chromatin modifiers are frequently seen in cancers. Here, the authors show that the chromatin accessibility regulator HMGN1 - which is frequently mutated by amplification in leukemias - acts by blocking myeloid differentiation.

Messenger RNA has received little attention as a potential therapeutic agent. Kormann et al. show that intramuscular injection of chemically modified erythropoietin mRNA substantially increases the hematocrit in mice and demonstrate the curative potential of pulmonary mRNA delivery in a mouse model of congenital surfactant protein B deficiency.

MPHOSPH8 loss inhibits acute myeloid leukemia (AML) development by reactivating LINE-1 retrotransposons. LINE-1 suppression is associated with therapy resistance and poor prognosis in patients with AML.

Hypothalamic melanocortin neurons control energy homoeostasis by modulating appetite. Here, the authors reveal a role for the transcription factor Tbx3 as a regulator of the peptidergic identity and function of immature and mature mouse melanocortin neurons.