This is the website of the Division of Gene Expression Dynamics, Medical Research Center Initiative for High Depth Omics, Medical Institute of Bioregulation, Kyushu University.

Using mouse embryonic stem (ES) cells as a model, we aim to elucidate the regulatory mechanism of a phenomenon called transcriptional bursting using a novel experimental approach that combines genome editing technology, live imaging, and cell biology. We are also working on elucidating the molecular mechanism of cell-to-cell heterogeneity in gene expression levels in mouse ES cells.

We are currently recruiting undergraduate, graduate students, and postdocs. If you would like to know more about our research and educational policies, please contact Ochiai.

NEWS

  • A protocol for DNA/RNA/IF-seqFISH image analysis has been published in Methods Mol. Biol.!
    The image analysis protocol for DNA/RNA/IF-seqFISH has been published in Methods Mol. Biol. (Computational Methods for 3D Genome Analysis, edited by Ryuichi Nakato)! https://link.springer.com/protocol/10.1007/978-1-0716-4136-1_24#DOI Image Analysis Protocol for DNA/RNA/Immunofluorescence (IF)-seqFISH DataHiroaki Ohishi & Hiroshi Ochiai AbstractImaging-based spatial multi-omics technologies enable the analysis of higher-order genomic structures, gene transcription, and the localization of proteins and posttranslational modifications (PTMs) at the single-allele level. This allows for detailed observation of biological phenomena, including transcription machinery within cells and tissues. This chapter provides an in-depth explanation of the principles behind these technologies, focusing on DNA/RNA/immunofluorescence (IF) sequential fluorescence in situ hybridization (seqFISH). The chapter also offers a comprehensive, step-by-step image analysis protocol, covering aspects such as image preprocessing, spot detection, and data visualization. For practical use, complete Jupyter Notebook codes are available on GitHub (https://github.com/Ochiai-Lab/seqFISH_analysis).
  • A collaborative study with the Mat Francois lab (Centenary Institute, The University of Sydney) has been published on bioRxiv!
    This research focuses on the complex molecular mechanisms required for stem cells to self-renew, shedding light on the dynamics of the SOX2 transcription factor. Using single-molecule tracking technology combined with the STREAMING-tag transcriptional reporter system, we visualized in real-time how SOX2 clusters form at the Nanog gene locus and their relationship to transcription bursts in embryonic stem cells. The study reveals that SOX2 clustering occurs at different timings from transcription bursts, highlighting distinct roles for SOX2 at various stages of the transcription cycle. https://www.biorxiv.org/content/10.1101/2024.09.10.612363v1 Anti-phase clustering of regulatory factors shapes gene bursting Bitong Li, Yew Yan Wong, Neftali Flores-Rodriguez, Tara Davidson, Matthew S Graus, Valeriia Smialkovska, Hiroaki Ohishi, Angelika Feldmann, Hiroshi Ochiai, Mathias Francois AbstractThe ability of stem cells to divide and self-renew depends on a complex choreography of molecular events that maintain the transcriptional oscillation of pluripotency genes. Only a handful of transcription factors (TFs) are necessary to preserve […]
  • A joint research paper with Kyushu University’s Institute of Medical Science, Ohkawa Laboratory, on the spatial omics technology “PECAb” has been published in Nature Communications!
    The Ohkawa Laboratory at the Medical Institute of Bioregulation, Kyushu University, has developed PECAbs (Precise Emission Canceling Antibodies) with cleavable fluorescent labels. PECAbs enable high-specificity sequential imaging using hundreds of antibodies, allowing for the reconstruction of spatiotemporal dynamics of signal transduction pathways. Furthermore, by combining this approach with continuous single-molecule RNA-FISH, it is possible to effectively classify cells within human tissues and identify their signal activation states. The PECAb system functions as a comprehensive platform for analyzing complex cellular processes. This content has been published in the journal Nature Communications. Title: Precise immunofluorescence canceling for highly multiplexed imaging to capture specific cell states Authors: Kosuke Tomimatsu, Takeru Fujii, Ryoma Bise, Kazufumi Hosoda, Yosuke Taniguchi, Hiroshi Ochiai, Hiroaki Ohishi, Kanta Ando, Ryoma Minami, Kaori Tanaka, Taro Tachibana, Seiichi Mori, Akihito Harada, Kazumitsu Maehara, Masao Nagasaki, Seiichi Uchida, Hiroshi Kimura, Masashi Narita & Yasuyuki Ohkawa Nature Communications, 15, 3657 (2024) https://www.nature.com/articles/s41467-024-47989-9
  • Our lab has just released a new preprint!
    Our lab has published a new preprint! It has been observed that in the state of transcriptional activation, distinctive higher-order genomic structures and protein aggregates are formed, furthermore, the viscosity around genes increases, and the interaction time between enhancers and promoters is prolonged. This research was conducted in collaboration with Drs. Hiroaki Ohishi (in our lab), Soya Shinkai (RIKEN), Shuichi Onami (RIKEN), Kazufumi Hosoda (Ansanga Labs), and Yasuyuki Ohkawa (MIB, Kyushu U.)! https://www.biorxiv.org/content/10.1101/2023.11.27.568629v1 Recent imaging analyses have revealed that transcription is a dynamic process that switches between an active state, where genes are continuously transcribed by RNA Polymerase II, and an inactive state where transcription does not occur. This is known as transcriptional bursting and is a universal phenomenon observed across many species and cell types. It has been shown that this transition involves the interaction between enhancers and promoters, as well as the assembly of transcriptional regulatory factors. Transcription […]
  • We have been selected for JST CREST (Bio-DX)!
    We have been selected for the JST CREST, “Innovation of Life Science through Digital Transformation Focused on Data-Driven and AI-Driven Technologies” (Bio-DX, Research Director: Professor Yasushi Okada). https://www.jst.go.jp/kisoken/crest/application/2023/230919/230919crest.pdf Research Project Title: Understanding the Mammalian Cell Fate Regulation Framework through Multimodal Spatiotemporal Integrated Omics Analysis. The lead researcher is Ochiai from Kyushu University. Main collaborators include Takuya Funatomi (Nara Institute of Science and Technology), Kazumitsu Maehara (Kyushu University Institute of Biodefense Medicine), and Soya Shinkai (RIKEN Center for Life Science Technologies). Research Overview: The process of mammalian development involves numerous stochastic elements and unknown factors, making a detailed understanding of the cell fate regulation mechanism challenging. In this research, we will target the early developmental stages of mice and organoids to analyze the heterogeneity in gene expression between cells, the epigenomic elements that regulate it, and intercellular interactions in a data-driven, multimodal, and spatiotemporal manner, elucidating the cell fate regulation mechanism. […]