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In this study, the authors present optimization and efficacy testing of apolipoprotein-based lipid nanoparticles for delivering various nucleic acid therapeutics in vivo to immune cells and their progenitors in the bone marrow.

Glioblastoma—the deadliest form of brain cancer—alters the calvarial bone and its marrow components, pushing it toward producing more myeloid cells and contributing to an immunosuppressive environment.

Bone marrow adipose tissue accounts for almost 10% of human fat mass, but its roles remain unclear. Here, Xu et al. identify more than 45 diseases linked to marrow adiposity in over 48,000 people, including causal roles in musculoskeletal disease.

Glucocorticoid (GC) induced osteoporosis (GIOP) remains a significant clinical problem. Here, the authors find that GCs disrupt skeletal stem cell–endothelial crosstalk via Basigin that can be targeted as a potential therapy for GIOP.

Laser ablation of imaged surface layers under adaptive control enables volumetric imaging of samples consisting of heterogeneous tissues, such as the skull and brain.

Meningeal immunity represents an emerging focus in neuroimmune interactions with implications for vaccine development. Here, the authors review how insights from meningeal immunity are being integrated into vaccine innovation, with implications for treating CNS tumors, infectious diseases, and age-related neuroinflammation.

Zhang, Lahry, Cipurko et al. show that the microbial metabolites queuine and preQ₁ modify the same host tRNA. PreQ₁-tRNA reduces cell proliferation, slows tumour growth, decreases the translation of ribosomal proteins and is cleaved by IRE1 on the ER ribosome.

In the randomized phase 3 AMPLITUDE trial, patients with HRR-deficient mCSPC experienced longer progression-free survival when they were treated with niraparib and AAP compared to placebo and AAP.

Hematopoiesis influences the progression of cardiovascular disease, yet the influence of cardiovascular disease on the bone vasculature is unknown. Hoffmann, Luxán, Abplanalp et al. describe the response of the bone cell composition to myocardial infarction and provide a rationale for using anti-inflammatory therapies to prevent the deterioration of the bone vascular niche

Tan and colleagues conducted a single-cell multiomic analysis of T cell acute lymphoblastic leukemia and identified a treatment-resistant subpopulation of bone marrow progenitor-like blasts associated with poor outcomes.

Yang and colleagues have previously reported a clinically guided culture method to generate allogeneic CAR-NKT cells by engineering human hematopoietic stem and progenitor cells. As potential application, here the authors describe the design and characterization of allogeneic CD33-targeting CAR-NKT cells, showing anti-tumor activity in preclinical models of bone marrow-resident myeloid malignancies.

Haematopoietic stem cell numbers are restricted at both systemic and local levels.

Ramadoss et al. show that bone-marrow-derived macrophages contribute to heart repair following myocardial infarction by secreting GPNMB, which binds to the orphan receptor GPR39 to improve myocyte contractility and reduce fibroblast activation.

Here, the authors develop a hybrid agent-based model to quantify the contributions of intrinsic cellular mechanisms and bone ecosystem factors to therapy resistance in multiple myeloma. They show that intrinsic mechanisms are essential for resistance, and that the bone microenvironment provides a protective niche that increases the likelihood.

A rhynchocephalian skeleton around 3–7 million years older than the oldest currently known lepidosaur fossil provides important insight into the origin of lizards and snakes.

The BabyScreen+ study offered genomic screening to 1,000 newborns in Australia, and showed that the approach is feasible and positively received by families, leading to molecular diagnoses in 1.6% of babies.

Neuroinflammation following intracortical microelectrode implantation impairs long-term brain-machine interface performance. Here, the authors developed a nanoparticle-based therapy that improves local hemostasis and delivers dexamethasone, reducing inflammation.

Li-Fraumeni syndrome is a cancer predisposition disorder caused by TP53 variants, but the way different TP53 variants contribute remains unclear. Here, the authors analyse TP53 mutagenesis datasets and identify five TP53 variant clusters that show associations with specific cancer patterns as well as potential clinical strategies.

Bone marrow adipose tissue accounts for over 10% of human fat mass. Here, Xu et al. use deep learning to measure marrow adiposity in over 45,000 people, and identify genes associated with altered bone marrow adiposity.

The thymus is sensitive to acute insults including infection, as well as to injury from chemotherapy and myeloablative conditioning before hematopoietic cell transplantation. Here, Granadier et al. describe a role for IL-18 in limiting thymic regeneration by stimulating NK cells, which then target thymic epithelial cells.

The rapid waning of SARS-CoV-2-specific serum antibodies observed after immunization with COVID-19 mRNA vaccines may be accounted for by the absence of long-lived plasma cells in the bone marrow specific for the virus.

In a phase 2 randomized control trial, intermittent senolytic therapy administered to postmenopausal women did not result in a reduction in the bone resorption marker, serum CTx, compared to control at 20 weeks.

Previously undescribed hierarchical arrangements in haematopoietic stem cells and their niches that mediate both regenerative potential and immune privilege are identified.

The ability to genetically modify haematopoietic stem cells would allow the durable treatment of a diverse range of genetic disorders but gene delivery to the bone marrow has not been achieved. Here lipid nanoparticles that target and deliver mRNA to 14 unique cells within the bone marrow are presented.

Zhang et al. show that bone marrow fatty acid metabolism fuels expanded leukocyte production after myocardial infarction and, based on mouse, pig and human data, suggest that lipolysis in marrow adipocytes provides fatty acids to hematopoietic stem cells.

Current limb salvage techniques for the treatment of the osteopathic non-unions still have several drawbacks that may prolong the duration of treatment. Here, Lin et al., propose using an osteoinductive (BMP-2 eluting) intramedullary and biodegradable implant to achieve early bony bridging and show that pin tract infection or docking site non-union can be avoided in experimental animal models of large bone defects.

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.

In vivo gene editing hinges on identifying an ideal delivery vehicle from numerous candidates. Here, authors establish the GFP-on mouse model capable of translating successful adenine base editing to a fluorescent readout thus enabling the rapid evaluation of genome editing delivery vehicles.

We demonstrate the role of the ligand-gated purinergic ion channel P2RX4 in maintaining mouse plasma cells in their bone marrow niche.

David Evans, Brent Richards and colleagues carried out a genome-wide association study in 142,487 individuals from the UK Biobank and identified 153 new loci associated with heel bone mineral density. They also conducted in vivo studies that implicated GPC6 and several other genes in osteoporosis.

Aguirre-Ghiso and colleagues report that bone-marrow-resident mesenchymal stem cells promote cancer dormancy through TGF-β family members.

Sick heart and vessels skew hematopoiesis toward inflammatory myeloid cells. Rhode et al. show that hypertension, atherosclerosis and myocardial infarction cause endothelial dysfunction in bone marrow (BM), which in return causes overproduction of inflammatory myeloid cells and systemic leukocytosis in mice. This process is mediated by VEGF signaling, IL-6 and versican production by the BM endothelium.

Fernando Rivadeneira and colleagues in the Genetic Factors for Osteoporosis Consortium report a large-scale meta-analysis identifying new loci associated with bone mineral density (BMD) and risk of fracture. Thirty-two new loci are found to be associated with BMD, and 6 loci confer higher risk for low-trauma bone fracture.

Eosinophils are traditional immune effectors involved in tissue homeostasis. In this study, eosinophils emerge as key regulators of bone homeostasis by interacting with osteoclasts, inhibiting their differentiation and pathological bone loss.