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Biology subjects

Tomimatsu, K.

Publications and source records attributed to Tomimatsu, K..

4 recordsLinked to original sources

MEGA-FISH: Multi-omics Extensible GPU-Accelerated FISH Processing Framework for Huge-Scale Spatial Omics

Spatial omics enables comprehensive mapping of cell types and states in their spatial context, providing profound insights into cellular communication and tissue organization. However, analyzing large tissue sections, especially crucial for clinical applications, remains a significant challenge due to the computational demands of current image processing methods. To overcome these limitations, we developed MEGA-FISH, a flexible, GPU-accelerated Python framework optimized for large-scale spatial omics image analysis. Benchmarking on simulated and tissue images demonstrated that MEGA-FISH achieved high accuracy in spot detection while significantly reducing processing times compared with established tools. The frameworks adaptable computational capabilities optimize resource allocation (e.g., GPU or multi-core CPU) for diverse tasks, and its scalable architecture enables integration with advanced imaging and segmentation techniques. By bridging cutting-edge imaging methods and single-cell analysis, MEGA-FISH provides an efficient platform for multi-modal analysis and advances research and clinical applications of spatial omics at organ and organism scales.

bioinformatics↗

Precise immunofluorescence canceling for highly multiplexed imaging capturing specific cell state

Cell states are regulated by the response of signaling pathways to receptor ligand-binding and inter-cellular interactions. High-resolution imaging has been attempted to explore the dynamics of these processes and, recently, multiplexed imaging has profiled cell states by achieving a comprehensive acquisition of spatial protein information from cells. However, the specificity of antibodies is still compromised when visualizing activated signals. Here, we developed Precise Emission Canceling Antibodies (PECAbs) that have cleavable fluorescent labeling. PECAbs enable high-specificity sequential imaging using hundreds of antibodies, allowing for reconstruction of the spatiotemporal dynamics of signaling pathways. Additionally, combining this approach with seq-smFISH can effectively classify cells and identify their signal activation states in human tissue. Overall, the PECAb system can serve as a comprehensive platform for analyzing complex cell processes.

cell biology↗

Modeling population size independent tissue epigenomes by ChIL-seq with single-thin sections

Recent advances in omics studies have enabled analysis at the single-cell level; however, methods for analyzing the whole cell of large organs and tissues remain challenging. Here, we developed a method named tsChIL to understand the diverse cellular dynamics at the tissue level using high-depth epigenomic data. tsChIL allowed the analysis of a single tissue section and could reproducibly acquire epigenomic profiles from several types of tissues, based on the distribution of target epigenomic states, tissue morphology, and number of cells. The proposed method enabled the independent evaluation of changes in cell populations and gene activation of cells in regenerating skeletal muscle tissues, using a statistical model of RNA polymerase II distribution on gene loci. Thus, the integrative analysis by tsChIL can elucidate in vivo cell-type dynamics of tissues.

molecular biology↗

NOTCH-mediated non-cell autonomous regulation of chromatinstructure during senescence

Senescent cells interact with the surrounding microenvironment achieving diverse functional outcomes. In addition to autocrine and paracrine signalling mediated by factors of the senescence-associated secretory phenotype, we have recently identified that NOTCH1 can drive lateral induction of a unique form of senescence in adjacent cells through specific induction of the NOTCH ligand JAG1. Here we show that NOTCH signalling can modulate chromatin structure both autonomously and non-autonomously. In addition to senescence-associated heterochromatic foci (SAHF), oncogenic RAS-induced senescent (RIS) cells in culture exhibit a massive increase in nucleosome-free regions (NRFs). NOTCH signalling suppresses both SAHF and NFR formation in this context. Strikingly, NOTCH-induced senescent cells, or cancer cells with high JAG1 expression, also drive similar chromatin architectural changes in adjacent cells through cell-cell contact. Mechanistically, we show that NOTCH signalling represses the chromatin architectural protein HMGA1, an association found in a range of human cancers. Thus, HMGA1 is involved not only in SAHFs, but also RIS-specific NFR formation. In conclusion, this study identifies that the JAG1-NOTCH-HMGA1 axis mediates the juxtacrine regulation of chromatin architecture.

cell biology↗