西亚试剂：Visualizing Spatiotemporal Dynamics of Multicellular Cell-C

Visualizing Spatiotemporal Dynamics of Multicellular Cell-Cycle Progression

Asako Sakaue-Sawano,1,3 Hiroshi Kurokawa,1,4 Toshifumi Morimura,2 Aki Hanyu,5 Hiroshi Hama,1 Hatsuki Osawa,1 Saori Kashiwagi,2 Kiyoko Fukami,4 Takaki Miyata,6 Hiroyuki Miyoshi,7 Takeshi Imamura,5 Masaharu Ogawa,2 Hisao Masai,8 and Atsushi Miyawaki1,3,

1 Laboratory for Cell Function and Dynamics, Advanced Technology Development Group, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama 351-0198, Japan
2 Laboratory for Cell Culture Development, Advanced Technology Development Group, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama 351-0198, Japan
3 Life Function and Dynamics, ERATO, JST, 2-1 Hirosawa, Wako-city, Saitama 351-0198, Japan
4 School of Life Science, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
5 Departments of Biochemistry, The Cancer Institute of the Japanese Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, Tokyo 135-8550, Japan
6 Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Syowa-ku, Nagoya, Aichi 466-8550, Japan
7 Subteam for Manipulation of Cell Fate, BioResource Center, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan
8 Genome Dynamics Project, Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan

Summary

The cell-cycle transition from G₁ to S phase has been difficult to visualize. We have harnessed antiphase oscillating proteins that mark cell-cycle transitions in order to develop genetically encoded fluorescent probes for this purpose. These probes effectively label individual G₁ phase nuclei red and those in S/G₂/M phases green. We were able to generate cultured cells and transgenic mice constitutively expressing the cell-cycle probes, in which every cell nucleus exhibits either red or green fluorescence. We performed time-lapse imaging to explore the spatiotemporal patterns of cell-cycle dynamics during the epithelial-mesenchymal transition of cultured cells, the migration and differentiation of neural progenitors in brain slices, and the development of tumors across blood vessels in live mice. These mice and cell lines will serve as model systems permitting unprecedented spatial and temporal resolution to help us better understand how the cell cycle is coordinated with various biological events.

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