Josep Carreras Leukaemia Research Institute

BackgroundThe integration of multimodal single-cell data enables comprehensive organ reference atlases, yet its impact remains largely unexplored, particularly in complex tissues. Using the kidney as an emblematic example of a complex organ, we perform a systematic evaluation of multimodal single-cell integration strategies, with heart tissue used for additional methodological validation.ResultsWe generate a benchmarking dataset for the renal cortex by integrating 3' and 5' scRNA-seq with joint snRNA-seq and snATAC-seq, profiling 119,744 high-quality nuclei/cells from 19 donors. To align cell identities and enable consistent comparisons, we develop the interpretable machine learning tool scOMM (single-cell Omics Multimodal Mapping) and systematically assess integration strategies. "Horizontal" integration of scRNA and snRNA-seq improves cell-type identification, while "vertical" integration of snRNA-seq and snATAC-seq has an additive effect, enhancing resolution in homogeneous populations and difficult-to-identify states. Global integration is especially effective in identifying adaptive states and rare cell types, including WFDC2-expressing Thick Ascending Limb and Norn cells, previously undetected in kidney atlases.ConclusionsOur work establishes a robust framework for multimodal reference atlas generation, advancing single-cell analysis and extending its applicability to diverse tissues.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13059-026-04002-4.

Endothelial dysfunction is central to COVID-19 pathophysiology, contributing to vascular complications and disease progression. However, the mechanisms driving disease evolution and response to endothelial-targeted therapies remain unclear. This study characterizes endothelial activation throughout the course of acute COVID-19 and evaluates the response to potential therapeutic agents.Serum samples from patients admitted due to moderate to severe COVID-19 pneumonia were prospectively collected on three study time points (+1 day, +4 days and +10 days). Human microvascular endothelial cells were cultured in medium supplemented with pooled serum within the same disease stage, with or without defibrotide, apixaban, or tocilizumab. Endothelial activation was assessed by immunofluorescence and quantitative mRNA expression of adhesion molecules, extracellular matrix (ECM) proteins, and innate immunity receptors. ECM reactivity was evaluated using a platelet adhesion assay. Intracellular signaling pathways were analyzed by immunoblotting.One-hundred and two patients were included. Compared to healthy donor plasma, patient plasma induced upregulation of Vascular cell adhesion molecule-1, Toll-like receptor 4, and von Willebrand factor in endothelial cells. This effect decreased over admission days and in response to drugs. Similarly, ECM reactivity was highest at admission and declined as the disease progressed. Vascular-endothelial cadherin was mildly downregulated, but its expression was unaffected by drug treatment in vitro. Defibrotide mitigated COVID-19 serum induced p38MAPK and Erk activation but enhanced Akt phosphorylation.Serum from severe COVID-19 patients induces a proinflammatory and prothrombotic endothelial phenotype, which can be modulated by endothelial-targeted therapies. These findings support the potential clinical value of endothelial-directed treatments.

Background/Objectives: Sirtuin 7 (SIRT7), a nuclear NAD+-dependent deacylase, plays multifaceted and sometimes opposing roles in tumorigenesis. By preserving chromatin architecture and genome integrity, SIRT7 protects against malignant transformation; however, once cancer is established, it can either sustain or restrain tumor growth through context-dependent signaling programs, albeit via largely unknown mechanisms. Recent findings have uncovered an additional—and previously underappreciated—dimension: SIRT7’s capacity to modulate anti-cancer immunity. This review revisits the current understanding of SIRT7 in cancer by emphasizing its emerging immunomodulatory functions and influence on the tumor microenvironment. Methods: We conducted a comprehensive literature review up to October 2025 using the PubMed database to identify both tumor-intrinsic and tumor-extrinsic mechanisms linking SIRT7 to anti-cancer immunity and to relate the established molecular functions of SIRT7—such as its roles in metabolism, genome maintenance, and inflammatory regulation—to immune regulation. Results: SIRT7 directly regulates immune checkpoint expression and T cell metabolic fitness, thereby positioning it as a key node connecting tumor-intrinsic programs with immune surveillance. Moreover, by controlling molecular pathways such as metabolism, genomic stability, and inflammatory responses—both within cancer cells and across other components of the tumor microenvironment—SIRT7 may more broadly influence the immune landscape, orchestrating immune evasion or recognition. Conclusions: Deciphering how SIRT7’s tumor-intrinsic and immunomodulatory functions intersect is essential for anticipating the consequences of its pharmacological targeting in cancer. A deeper understanding of this interplay will enable the rational design of combination strategies that integrate SIRT7 modulation with immunotherapy within a precision medicine framework.