RIKEN

Hiroshima University

The University of Tokyo

Summary of presentation

A joint research group led by Dr. Tomonobu Watanabe, Team Leader of the Advanced Bioimaging Research Team at the RIKEN Center for Frontier Biosciences, Dr. Yasushi Okada, Team Leader of the Cell Polarity Control Research Team, Dr. Yasushi Okada, Professor at the Graduate School of Medicine, The University of Tokyo and Assistant Professor at the Graduate School of Science, Hiroshima University, and Assistant Professor Okamoto at the Amphibian Research Center, Hiroshima University, has quantitatively analyzed the behavior of transcription factors (Nanog, Oct4) acting in mouse ES cells with single molecule precision. Assistant Professor Kazuko Okamoto of the Amphibian Research Center at Hiroshima University and her colleagues have quantitatively analyzed the behavior of transcription factors (Nanog and Oct4) working in mouse ES cells with single molecule precision and discovered a new mechanism for maintaining the pluripotency of differentiated ES cells.

The research results are expected to provide new insights into the field of stem cell research, as well as contribute to improving the efficiency of iPS cell production and stabilizing the quality of iPS cells.

ES cells have the ability to differentiate into any cell type in the body (pluripotency), and Nanog and Oct4 are transcription factors that are essential for ES cells to maintain pluripotency and promote their own expression as well as each other's expression. Until now, the relationship between the intracellular molecular dynamics of Nanog and Oct4, changes in chromatin structure, and differentiation pluripotency has not been clarified.

In this study, the research group used a special microscope that can observe the movement of a single protein molecule to observe the movement of Nanog and Oct4 at the moment of mouse ES cell differentiation with single-molecule precision, and quantified various characteristics of their physical behavior, including residence time and frequency on DNA. The analysis revealed new correlations, such as the fact that Nanog stays on DNA longer once differentiation begins, and led to the proposal of a new "negative feedback mechanism" in which Nanog and Oct4 cooperate to regulate ES cell differentiation so that it does not proceed too far.

This research was published in the online edition of the scientific journal The EMBO Journal (August 23: Japan Standard Time).

Schematic diagram showing the flow of this research

For more information, please visit the RIKEN website.

Journals

Journal name	The EMBO Journal
Title of paper	Single-molecule tracking of Nanog and Oct4 in living mouse embryonic stem cells uncovers a feedback mechanism of pluripotency maintenance
DOI number	10.15252/embj.2022112305