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Organoids in Genetic Disorders: from Disease Modeling to Translational Applications
Stem Cell Rev Rep. 2025 Sep 11. doi: 10.1007/s12015-025-10973-x. Online ahead of print.
ABSTRACT
The emergence of organoid models has significantly bridged the gap between traditional cell cultures/animal models and authentic human disease states, particularly for genetic disorders, where their inherent genetic fidelity enables more biologically relevant research directions and enhances translational validity. This review systematically analyzes established organoid models of genetic diseases across organs (e.g., brain, eye, kidney, lung, and heart), highlighting their pivotal roles in identifying novel pathogenic genes, elucidating disease mechanisms, and advancing therapeutic strategies such as drug screening platforms, gene-editing therapies, and organ transplantation strategies. Furthermore, we critically address current limitations-including challenges in recapitulating complex pathologies and scaling production-while underscoring their potential for personalized medicine through multi-omics integration and bioengineering innovations. Although the scope of "genetic diseases" is broad, this synthesis focuses on disorders with well-defined inheritance patterns, such as monogenic disorders, copy number variations (CNVs), and aneuploidies. Despite covering only a subset of these conditions, this review aims to provide researchers with a comprehensive overview of the field, emphasizing how organoid-based approaches could accelerate both mechanistic discoveries and clinical translation in genetic disease research.
PMID:40931310 | DOI:10.1007/s12015-025-10973-x
Thor: a platform for cell-level investigation of spatial transcriptomics and histology
Nat Commun. 2025 Aug 5;16(1):7178. doi: 10.1038/s41467-025-62593-1.
ABSTRACT
Spatial transcriptomics links gene expression with tissue morphology, however, current tools often prioritize genomic analysis, lacking integrated image interpretation. To address this, we present Thor, a comprehensive platform for cell-level analysis of spatial transcriptomics and histological images. Thor employs an anti-shrinking Markov diffusion method to infer single-cell spatial transcriptome from spot-level data, effectively combining gene expression and cell morphology. The platform includes 10 modular tools for genomic and image-based analysis, and is paired with Mjolnir, a web-based interface for interactive exploration of gigapixel images. Thor is validated on simulated data and multiple spatial platforms (ISH, MERFISH, Xenium, Stereo-seq). Thor characterizes regenerative signatures in heart failure, screens breast cancer hallmarks, resolves fine layers in mouse olfactory bulb, and annotates fibrotic heart tissue. In high-resolution Visium HD data, it enhances spatial gene patterns aligned with histology. By bridging transcriptomic and histological analysis, Thor enables holistic tissue interpretation in spatial biology.
PMID:40764306 | PMC:PMC12325965 | DOI:10.1038/s41467-025-62593-1
Purine salvage–associated metabolites as biomarkers for early diagnosis of esophageal squamous cell carcinoma: a diagnostic model–based study
Cell Death Discovery, Published online: 14 March 2024; doi:10.1038/s41420-024-01896-6
Purine salvage–associated metabolites as biomarkers for early diagnosis of esophageal squamous cell carcinoma: a diagnostic model–based study