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KAIST Predicts Diseases by Early Detection of Aging Signals in Liver Tissue - KAIST-KRIBB Develops ‘FiNi-seq’ Technology to Capture Characteristics of Fibrotic Microenvironments Accumulated in Liver Tissue and Dynamic Changes of Early Aging Cells - Elucidation of the Spatial Ecosystem of Aged Liver Tissue, where Reprogramming of Senescent Cells and Immune Exhaustion Progresses, at the Single-Cell Genome and Epigenome Levels < (From left) Professor Jong-Eun Park of KAIST Graduate School of Medical Science and Engineering (GSMSE), Dr. Chuna Kim of KRIBB, Dr. Kwon Yong Tak of KAIST GSMSE, Ph.D. Candidate Juyeon Kim of KRIBB, Ph.D. Candidate Myungsun Park of KAIST GSMSE > Aging and chronic diseases involve the gradual accumulation of subtle tissue changes over a long period. Therefore, there are still limitations in quantitatively understanding these changes within organs and linking them to early signs of disease onset. In response, Korean researchers have successfully developed a platform technology that accurately captures localized changes that first occur within tissue, significantly aiding in faster disease discovery and prediction, and in setting personalized treatment targets. KAIST (President Kwang Hyung Lee) announced on June 12th that a joint research team led by Professor Jong-Eun Park of the Graduate School of Medical Science and Engineering at KAIST and Dr. Chuna Kim of the Aging Convergence Research Center at the Korea Research Institute of Bioscience and Biotechnology (KRIBB, President Seok-Yoon Kwon) has developed ‘FiNi-seq (Fibrotic Niche enrichment sequencing)’ technology. This technology captures fibrotic microenvironments locally occurring in aged liver tissue and enables precise analysis at the single-cell transcriptome level*. *Single-cell transcriptome analysis: A method to measure how actively each cell uses which genes, allowing identification and function of individual diseased cells. The researchers developed a method to selectively enrich early aging microenvironments where regeneration is delayed and fibrosis accumulates, by physically selecting regions with high tissue degradation resistance in aged liver tissue. In this process, high-resolution identification of fibrosis-related endothelial cells, fibroblasts interacting with the immune system, and immune-exhausted cells such as PD-1 highly expressing CD8 T cells, which were difficult to capture with existing single-cell analysis technologies, was possible. In particular, the research team confirmed through ‘FiNi-seq’ technology that specific cells observed in fibrotic areas within aged liver tissue secondarily age the surrounding environment through secreted factors, and that this leads to the expansion of the aged environment. Furthermore, they also elucidated the mechanism by which endothelial cells lose their tissue-specific identity and induce innate immune responses, promoting immune cell infiltration. Through spatial transcriptome analysis, the spatial distribution of fibroblasts interacting with immune cells was quantified, revealing their involvement in tissue regeneration, induction of inflammatory responses, and progression to chronic fibrosis. The research team performed integrated analysis of multi-omics\* data to obtain transcriptome and epigenome information, precisely interpreting the microenvironment of aged liver tissue and its spatial heterogeneity, and confirming how these changes are connected to the intrahepatic vascular structure. *Multi-omics: An integrated analysis method for various biological information within an organism, such as genes, proteins, metabolites, and cell information. The newly developed ‘FiNi-seq’ technology is expected to be a useful platform for high-resolution capture of pathophysiological signals in most chronic liver diseases, including the aging process that causes fibrosis. < Figure 1. Isolation of fibrotic regions from aged liver tissue, followed by single-cell transcriptome analysis and validation in a fibrosis model. > The first author, Dr. Kwon Yong Tak of KAIST Graduate School of Medical Science and Engineering (GSMSE), a hepatologist at Seoul St. Mary's Hospital, designed this study to lay the groundwork for early diagnosis and treatment of fibrosis progression, the most important clinical prognostic indicator in chronic liver disease, while pursuing his Ph.D. at KAIST KAIST GSMSE with support from the physician-scientist training program. Co-first author Myungsun Park, a Ph.D. candidate at KAIST KAIST GSMSE, was responsible for the technical implementation of FiNi-seq technology, and Juyeon Kim, a Ph.D. candidate at KRIBB's Aging Convergence Research Center, was responsible for imaging analysis of aged tissue, playing a key role in the research. Dr. Chuna Kim of KRIBB stated, “Through this study, we were able to precisely elucidate the cellular composition and spatial characteristics of the fibrotic microenvironment observed in aged liver tissue at the single-cell level.” < Figure 2. Spatially defined stepwise progression patterns of aging-related regions within the liver and identification of regulatory factors inducing them. > Professor Jong-Eun Park of the Graduate School of Medical Science and Engineering said, “As an analytical technology that can capture subtle changes occurring in the early stages of aging and chronic diseases, it is expected to play a significant role in finding effective treatment targets in the future. Also, we plan to expand this research to chronic diseases in other organs such as the lungs and kidneys, as well as various liver disease models.” This research was published in the international journal ‘Nature Aging’ on May 5, 2025, with Dr. Kwon Yong Tak of KAIST KAIST GSMSE, Ph.D. Candidate Juyeon Kim of KRIBB, and Ph.D. Candidate Myungsun Park of KAIST as co-first authors. *Paper Title: Quasi-spatial single-cell transcriptome based on physical tissue properties defines early aging associated niche in liver *DOI: https://doi.org/10.1038/s43587-025-00857-7 This research was supported by several domestic institutions, including the National Research Foundation of Korea, the Korea Health Industry Development Institute (KHIDI), the Korea Research Institute of Bioscience and Biotechnology (KRIBB), KIST, POSCO Science Fellowship, and the Convergence Medical Scientist Training Program.
2025.06.12 View 6824