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A multiomics single-cell atlas of the human maternal–fetal interface including the myometrium, combining spatial transcriptomics data with chromatin accessibility, provides a comprehensive analysis of cell states as placental cells infiltrate the uterus during early pregnancy.

Here, the authors develop pluripotent stem cell-derived kidney organoids by mimicking in vivo proximal differentiation, providing a model to study nephron development, injury responses, and a platform for therapeutic discovery.

Oncofetal (OnF) reprogramming, driven by YAP and AP-1, induces phenotypic plasticity and therapy resistance in WNT-dependent colorectal cancer (CRC). Targeting the OnF state in combination with chemotherapy substantially attenuates tumor growth in mouse models and patient-derived CRC tumoroids.

The control of translation during mitosis has an important role in cancer cell biology. Here the authors report that in mitotically arrested cancer cells, redistribution of ribosomes towards upstream open reading frames results in enhanced presentation of immunogenic peptides on cancer cell surface.

The organizer is a signaling center in the embryo that orchestrates the formation of body axes. Here they show that Hensen’s Node contains two main cell types and that changes in their abundance alter its ability to induce head versus trunk structures.

Mucosal melanoma (MM) is a cancer with poor prognosis derived from mucosal melanocytes. Here, the authors implement a combination of genetic changes that occur in MM patients in a zebrafish model, revealing the potential MM cell of origin and showing that patient and zebrafish MMs share a gene signature that is more metastatic and immune-evasive.

Together with a companion paper, the generation of a transcriptomic atlas for the mouse lemur and analyses of example cell types establish this animal as a molecularly tractable primate model organism.

Lizards are the closest known relatives of mammals capable of epimorphic tail regrowth. Here, single-cell analysis of regenerating lizard tails reveals a phagocyte-induced fibroblast population contributing to blastema formation and chondrogenesis.

PD-1 is a critical modulator of CD8⁺ T cell activation and exhaustion. Sen and colleagues show that a cell-state-specific enhancer tunes PD-1 expression exclusively in exhaustion and that deletion of this enhancer improves CD8⁺ T cell function.

Synthetic Notch (synNotch) receptors are genetically encoded, modular synthetic receptors that enable mammalian cells to detect environmental signals and respond by activating user-prescribed transcriptional programs. Here the authors apply synNotch receptors to spatially control differentiation of endothelial and skeletal muscle cells in a multicellular construct on assorted biomaterials.

The use of single cell sequencing has enabled more detailed analysis of the immune response to infection. Here the authors characterise the immune response to malaria infection in an endemic region using single cell transcriptomics indicating regulatory signatures associated with infection.

Microscopic colitis is a chronic inflammatory disease of the large intestine. Here the authors use single-cell RNA transcriptomic profiling and tissue localization studies to characterise the colon immune cell populations in MC, showing expansion of CD8 T cells with diverse TCR clonotypes and expression of CD4 T reg cell signatures.

Derivation of human primordial germ cell-like cells (hPGCLCs) is critical for reproductive medicine. Here, authors report the induction of hPGCLCs in a bioengineered human pluripotent stem cell culture that mimics peri-implantation human development.

CD4⁺ T cells are known to be important in Plasmodium infection. Here the authors use mouse models to track antigen-experienced TCR transgenic and polyclonal CD4⁺ T cells during Plasmodium re-infection, and show different T cell phenotypes and varied responses in different areas of the spleen.

Naked mole-rats are long-lived rodents with remarkable resistance to cancer. Here authors show that their T-cell compartment is different from that of mice in that they have a large population of circulating cytotoxic γδ T cells harboring a dominant clonotype, and the clonotypic diversity of their conventional cytotoxic αβ T cells is more modest than that of mice.

Here the authors use positron emission tomography to visualize fibroblasts in patients with arthritis and combined with spatial transcriptomic data show that these cells undergo a phenotypic shift upon resolution of inflammation. A CD200⁺DKK3⁺ fibroblast subset promotes this resolution by inhibiting tumor necrosis factor and interleukin-17A.

The autophagy proteins Beclin 1 and FIP200, but not other essential autophagy components, such as ATG5, ATG16L1 or ATG7, regulate quiescence of tissue-resident macrophages, thereby modulating immune activation and resistance to Listeria monocytogenes infection.

A survey of the CD4⁺ T cells in human melanomas indicates that immune evasion is mediated through direct stimulation of neoantigen-specific tumour-reactive regulatory T cells by HLA class II-positive melanoma cells.

An examination of motor cortex in humans, marmosets and mice reveals a generally conserved cellular makeup that is likely to extend to many mammalian species, but also differences in gene expression, DNA methylation and chromatin state that lead to species-dependent specializations.

Abdominal adhesions are a common cause of bowel obstruction, but knowledge regarding adhesion biology and anti-adhesion therapies remains limited. Here the authors report a systematic analysis of mouse and human adhesion tissues demonstrating that visceral fibroblast JUN and associated PDGFRA expression promote adhesions, and JUN suppression can prevent adhesion formation.

Amyloid-like proteins are central to age-related diseases, such as Alzheimer’s and Parkinson’s. Here, the authors show that transcription errors can produce mutant proteins with enhanced amyloid- and prion-like properties in human cells.

Horitani, Chavkin et al. report that the loss of the Y chromosome in macrophages from failing human hearts correlates with cardiac fibroblast activation and that the deficiency of a single Y chromosome gene, Uty, triggers an epigenetic rewiring in macrophages toward a profibrotic phenotype and increases cardiac fibrosis and dysfunction that can be prevented by TGFβ-neutralizing antibodies.

Colonna and colleagues show that the transcription factor Aiolos controls chromatin accessibility and histone acetylation at genes linked to the activation of intestinal intraepithelial lymphocytes.

Pathogens often persist within granulomas which form to control infection. Here, Harvest et al describe an innate granuloma that eradicates a ubiquitous environmental pathogen without inducing adaptive immunity.

Osteolytic lesions (OL) are frequent in multiple myeloma (MM), but are poorly understood. Here, the authors characterise OLs in MM patient samples using single-cell RNA-seq, revealing genes that are specifically regulated in OL compared to random bone marrow aspirates and that reflect the response to induction therapy.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

While metabolic reprogramming has been shown to drive changes in cell identity, the link between cellular metabolism and gene expression remains poorly characterized. Here they show that histone lactylation couples metabolism and transcription during neural crest cell differentiation in the early embryo.

Donor-derived, EBV-specific CD8⁺ T cells engineered to express a high-affinity WT1-specific TCR established persistent T cell responses that safely prevented post-HCT relapse in patients with high-risk AML.

Despite recent progress to advance cardiac cell-based therapy for patients, heart failure mortality rivals most cancers. Here, the authors describe an approach to control and pattern 3 distinct human cardiac cell populations to promote superior repair and regeneration after myocardial infarction.

Analysing the regulatory consequences of mutations and splice variants at large scale in cancer requires efficient computational tools. Here, the authors develop RegTools, a software package that can identify splice-associated variants from large-scale genomics and transcriptomics data with efficiency and flexibility.

As pregnant women are considered vulnerable to SARSCoV-2 infection, it is important to investigate the actual risks involved. The authors show here that, while a T cell-dominant inflammatory response is observed at the maternal-foetal interface, the virus remains undetectable in the placenta but triggers specific immune responses in the neonatal (umbilical cord blood) circulation.

Hundreds of mutations in the gene CFTR lead to cystic fibrosis and represent a challenge to developing therapeutics. Here, authors demonstrate the ability of airway cells derived from human iPSCs to model genotype-specific CFTR function as well as pharmacologic rescue of disease causing mutations.

Human induced pluripotent stem cell-derived intestinal organoids (HIOs) are powerful tools to study development and diseases of the gastrointestinal tract. Here, the authors develop a directed differentiation protocol to generate mesenchyme-free HIOs that can be patterned towards proximal small intestine or colonic epithelium, and demonstrated their utility in modeling CFTR function.

Endocrinologists have traditionally focused on studying one hormone or organ system at a time. Here the authors use transcriptomic data from the mouse lemur to globally characterize primate hormonal signaling, describing hormone sources and targets, identifying conserved and primate specific regulation, and elucidating principles of the network.

In this study, Vande Voorde et al. investigate the potential of untargeted metabolomics as a stratification tool for colorectal cancer (CRC). They present a comprehensive pipeline to uncover metabolic vulnerabilities in CRC based on its genetic origin. With this approach, they show perturbations in methionine metabolism linked to APC deficiency, and identify adenosylhomocysteinase as an actionable therapeutic target.

CD4⁺ T cells are critical for effective responses to infection with the malaria parasite. Haque and colleagues use single-cell RNA sequencing and computational modeling to track T cell memory development during experimental Plasmodium infection of mice.

Deep-water coral frameworks may be an important and understudied source of biodiversity in the Red Sea, according to habitat suitability modelling generated using video imagery and in-situ coral sampling.

Raychaudhuri and colleagues use high-dimensional single-cell analysis of T cells from a human tuberculosis progression cohort. They identify a T_H17–like cluster reactive to Mycobacterium tuberculosis peptides that is reduced in people who previously progressed to active disease.

High-coverage, ultra-long-read nanopore sequencing is used to create a new human genome assembly that improves on the coverage and accuracy of the current reference (GRCh38) and includes the gap-free, telomere-to-telomere sequence of the X chromosome.

Free-living foraminiferal-algal nodules can be over 2000 years old and contribute 980 megatons of calcium carbonate to the mesophotic benthic carbonate budget of the NEOM region of the Saudi Arabian Red Sea, according to radiometric dating of nodule accretion rates and benthic surveys.

Broughton et al. report differences between rodent and large mammals with respect to ploidy of the cardiac interstitial cell population. These species-specific differences in ploidy of cardiac interstitial cells suggest potential challenges in extrapolating myocardial preclinical studies from rodent to large mammals.