Transcriptome Analysis by RNA Sequencing of Mouse Embryonic Stem Cells Stocked on International Space Station for 1584 Days in Frozen State after Culture on the Ground

Author:

Yoshida Kayo1,Hada Megumi2ORCID,Hayashi Masami1,Kizu Akane1,Kitada Kohei1,Eguchi-Kasai Kiyomi3,Kokubo Toshiaki3,Teramura Takeshi4,Hashizume Suzuki Hiromi5,Watanabe Hitomi6,Kondoh Gen6,Nagamatsu Aiko7,Saganti Premkumar2,Muratani Masafumi8,Cucinotta Francis A.9,Morita Takashi1

Affiliation:

1. Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan

2. Radiation Institute for Science and Engineering, Prairie View A&M University, Prairie View, TX 77446, USA

3. QST National Institute of Radiation Sciences (NIRS), Chiba 263-0024, Japan

4. Faculty of Medicine, Kindai University, Osaka 577-8502, Japan

5. Japan Space Forum (JSF), Tokyo 101-0062, Japan

6. Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8501, Japan

7. Japan Aerospace Exploration Agency (JAXA), Tsukuba 305-8505, Japan

8. Department of Genome Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan

9. Department of Health Physics and Diagnostic Sciences, University of Nevada, Las Vegas, NV 89154, USA

Abstract

As a space project, in “Stem Cells” by the Japan Aerospace Exploration Agency (JAXA), frozen mouse ES cells were stored on the International Space Station (ISS) in the Minus Eighty Degree Laboratory Freezer for ISS (MELFI) for 1584 days. After taking these cells back to the ground, the cells were thawed and cultured, and their gene expressions were comprehensively analyzed using RNA sequencing in order to elucidate the early response of the cells to long-time exposure to space radiation consisting of various ionized particles. The comparisons of gene expression involved in double-stranded break (DSB) repair were examined. The expressions of most of the genes that were involved in homologous recombination (HR) and non-homologous end joining (NHEJ) were not significantly changed between the ISS-stocked cells and ground-stocked control cells. However, the transcription of Trp53inp1 (tumor protein 53 induced nuclear protein-1), Cdkn1a (p21), and Mdm2 genes increased in ISS-stocked cells as well as Fe ion-irradiated cells compared to control cells. This suggests that accumulated DNA damage caused by space radiation exposure would activate these genes, which are involved in cell cycle arrest for repair and apoptosis in a p53-dependent or -independent manner, in order to prevent cells with damaged genomes from proliferating and forming tumors.

Funder

JAXA

QST-HIMAC

Ministry of Education, Culture, Sports, Science and Technology of Japan

Publisher

MDPI AG

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