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Spatial omics technologies enable a deeper understanding of cellular organizations and interactions within a tissue of interest. These assays can identify specific compartments or regions in a tissue with differential transcript or protein abundance, delineate their interactions, and complement other methods in defining cellular phenotypes. A variety of spatial methodologies are being developed and commercialized; however, these techniques differ in spatial resolution, multiplexing capability, scale/throughput, and coverage. Here, we review the current and prospective landscape of single cell to subcellular resolution spatial omics technologies and analysis tools to provide a comprehensive picture for both research and clinical applications.

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Multiplexed imaging and spatial transcriptomics enable highly resolved spatial characterization of cellular phenotypes, but still largely depend on laborious manual annotation to understand higher-order patterns of tissue organization. As a result, higher-order patterns of tissue organization are poorly understood and not systematically connected to disease pathology or clinical outcomes. To address this gap, we developed UTAG, a novel method to identify and quantify microanatomical tissue structures in multiplexed images without human intervention. Our method combines information on cellular phenotypes with the physical proximity of cells to accurately identify organ-specific microanatomical domains in healthy and diseased tissue. We apply our method to various types of images across physiological and disease states to show that it can consistently detect higher level architectures in human organs, quantify structural differences between healthy and diseased tissue, and reveal tissue organization patterns with relevance to clinical outcomes in cancer patients.

SARS-CoV-2 infection can manifest as a wide range of respiratory and systemic symptoms well after the acute phase of infection in over 50% of patients. Key questions remain on the long-term effects of infection on tissue pathology in recovered COVID-19 patients. To address these questions we performed multiplexed imaging of post-mortem lung tissue from 12 individuals who died post-acute COVID-19 (PC) and compare them to lung tissue from patients who died during the acute phase of COVID-19, or patients who died with idiopathic pulmonary fibrosis (IPF), and otherwise healthy lung tissue. We find evidence of viral presence in the lung up to 359 days after the acute phase of disease, including in patients with negative nasopharyngeal swab tests. The lung of PC patients are characterized by the accumulation of senescent alveolar type 2 cells, fibrosis with hypervascularization of peribronchial areas and alveolar septa, as the most pronounced pathophysiological features. At the cellular level, lung disease of PC patients, while distinct, shares pathological features with the chronic pulmonary disease of IPF. which may help rationalize interventions for PC patients. Altogether, this study provides an important foundation for the understanding of the long-term effects of SARS-CoV-2 pulmonary infection at the microanatomical, cellular, and molecular level.

Background Insulin feedback is a critical mechanism responsible for poor clinical efficacy of PI3K inhibition in cancer, and hyperglycemia is an independent factor associated with poor prognosis in glioblastoma. We investigated combination anti-hyperglycemic therapy in a mouse model of glioblastoma and evaluated the association of glycemic control in clinical trial data from patients with glioblastoma. Methods The effect of the anti-hyperglycemic regimens metformin and the ketogenic diet were evaluated in combination with PI3K inhibition in patient-derived glioblastoma cells and an orthotopic glioblastoma mouse model. Insulin feedback and the immune microenvironment were retrospectively evaluated in blood and tumor tissue from a Phase 2 clinical trial of buparlisib in patients with recurrent glioblastoma. Results We found that PI3K inhibition induces hyperglycemia and hyperinsulinemia in mice and that combining metformin with PI3K inhibition improves treatment efficacy in an orthotopic glioblastoma xenograft model. Through examination of clinical trial data, we found that hyperglycemia was an independent factor associated with poor progression-free survival in patients with glioblastoma. We also found that PI3K inhibition increased insulin receptor activation and T cell and microglia abundance in tumor tissue from these patients. Conclusion Reducing insulin feedback improves the efficacy of PI3K inhibition in glioblastoma in mice, and hyperglycemia worsens progression-free survival in patients with glioblastoma treated with PI3K inhibition. These findings indicate that hyperglycemia is a critical resistance mechanism associated with PI3K inhibition in glioblastoma and that anti-hyperglycemic therapy may enhance PI3K inhibitor efficacy in glioblastoma patients.

Overgrowth syndromes generally present with inherent health concerns and, in some instances, an increased risk of malignant intra-abdominal tumors, such as Wilms tumor or hepatoblastoma. There are various types of hyperplasia, but the crossed type is reported to be the rarest. We present a rare, crossed type of congenital hemihyperplasia. A six-year-old girl was referred to our clinic for leg length discrepancy and was diagnosed with congenital hemihyperplasia of the right lower limb and left upper limb. The leg length discrepancy had begun to affect the patient’s gait and stair climbing. We regularly monitored her leg length and checked for functional and cosmetic problems for 24 months. However, the hyperplasia progressed and caused severe gait impairment. Leg length discrepancy at the last check-up was 30 mm. She underwent femoral lengthening surgery using a monolateral external fixator. At the 14th month follow-up, her gait and stair climbing had greatly improved, and a scanogram revealed that the leg length discrepancy had been successfully treated with a mild varus angulation of the femur. We present a rare, crossed congenital hemihyperplasia. We recommend limb lengthening surgery for treating patients with idiopathic hemihyperplasia.