Issues

Summary: The ISSCR provides comprehensive guidelines and standards for using human stem cells in biomedical research. Here, we discuss how and why these should be incorporated in disease modeling research.

Summary: Radiotherapy for pancreatic cancer management is the subject of ongoing debate. We discuss how the lack of preclinical work assessing its impact in the tumour microenvironment may be restricting progress.

Summary: This At a Glance article reviews how biological resilience mechanisms act across scales to protect organisms from harmful insults, focusing on the challenges and opportunities for harnessing this remarkable phenomenon therapeutically.

Summary: Pathogenic mycobacteria establish infections by evading host immune defences. The amoeba Dictyostelium discoideum infected with Mycobacterium marinum is an innovative model to investigate key mycobacterial virulence pathways and host responses.

Summary: Interleukin-18 is a key cytokine in clinical cases of macrophage activation syndrome (MAS). Inhibition of the NLRP3 inflammasome reduces plasma levels of interleukin-18 but does not alleviate clinical features of MAS in mice.

Summary: A CRISPR/Cas9-based mouse model of MECP2 duplication syndrome mirrors IRAK1-MECP2 tandem duplications in patients, shedding light on neurobehavioral and immune complexities for therapeutic exploration.

Summary: Male germ cell-associated kinase (Mak) is a cilium-associated serine/threonine kinase that promotes axoneme development during ciliogenesis in zebrafish photoreceptors to ensure intracellular protein transport and photoreceptor survival.

Summary: Streptococcus pseudopneumoniae disrupts vocal fold epithelial integrity and function via the exported products HtrA1 and pneumolysin. These effects are mitigated in the presence of Streptococcus salivarius, a laryngeal commensal.

Editor's choice: Modeling of triple-negative breast cancer (TNBC) is challenging owing to the predominance of copy number variations. Here, we combined computational and Drosophila modeling to develop a database of functional drivers.

Summary: A mouse model of YES kinase-driven hepatocellular carcinoma recapitulates the pathophysiological features of clinically aggressive metastatic forms of this cancer and is useful for the preclinical evaluation of hepatocellular carcinoma therapies.

Summary: First multi-omics characterization of lung tissue in a clinically relevant pig model of insulin-deficient diabetes showed pronounced derangements in proteomic and metabolomic profiles, pointing to pulmonary complications.

Summary: A human regionalized neural organoid model for pontocerebellar hypoplasia, an ultra-rare neurological disorder, provides the foundation to decipher the brain region-specific disease mechanism in vitro.

Summary: Variants in TAF1 cause X-linked intellectual disability and X-linked dystonia–parkinsonism. A novel conditional cre-lox allele and ubiquitous knockout mouse model for Taf1 can be used to study TAF1 disease.