Development of single-cell spatial transcriptome analysis technology and elucidation of disease pathology.

Abstract

Various diseases, including epilepsy and cancer, arise from complex cellular and molecular changes. Recent advancements in disease research stem from "omics analysis" technology, which thoroughly analyzes gene/protein expression, genomic mutations, and chromatin modifications. Notably, single-cell RNA sequencing captures complete gene expression in individual cells, revealing molecular changes associated with diseases. However, traditional methods require cell separation, sacrificing spatial information essential for understanding pathology, especially where healthy and diseased tissues coexist. The development of spatial transcriptome technology in the 2020s allows for comprehensive gene expression analysis at the single-cell level while preserving spatial context. This emerging technology requires further development, particularly in Japan, where its adoption is limited and needs large-scale efforts beyond individual labs. This research project aims to enhance analytical expertise by collaborating across 6 National Centers (NCs), focusing on developing single-cell spatial transcriptomes and related methodologies, with the National Center of Neurology and Psychiatry leading the effort. We plan to apply our expertise to elucidate the pathogenesis of challenging diseases and aim to strengthen horizontal collaboration among the 6 NCs to build a global foundation in disease research.

Image

Perspectives

Construction and provision of a world-leading spatial transcriptome analysis platform that can be used jointly by 6NC
Elucidation of the pathology of diseases targeted by each NC through multi-modal omics analysis
Strengthening research capabilities and fostering young researchers through closer collaboration between the 6NCs

Comments from principal researcher

Mikio Hoshino
Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP

Despite the many years of research by many researchers to date, there are still many diseases that have not yet been overcome, and some kind of breakthrough was awaited. In this research, we aim to elucidate the pathogenesis of many intractable diseases and develop treatments by performing world-leading Xenium single-cell spatial transcriptome analysis and various single-cell omics analyses that could lead to a breakthrough.

Shared Researchers

Division of Brain Tumor Translational Research, National Cancer Center Research Institute (NCC)

Hiromichi Suzuki

Department of Vascular Physiology, National Cerebral and Cardiovascular Center,Research Institute (NCVC)

Yoshikazu Nakaoka

Division of Developmental Genomics, Department of Maternal-Fetal Biology, National Center for Child Health and Development (NCCHD)

Kazuhiko Nakabayashi

Department of Diabetes, Endocrinology, and Metabolism, National Center for Global Health and Medicine (NCGM)

Ryotaro Bouchi

Department of Neurogenetics, National Center for Geriatrics and Gerontology (NCGG)

Koichi Iijima