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Hematopoietic Transfer of the Anti-Cancer and Lifespan-Extending Capabilities of A Genetically Engineered Blood System

Jing-Ping Wang, View ORCID ProfileChun-Hao Hung, Yao-Huei Liou, Ching-Chen Liu, Kun-Hai Yeh, Keh-Yang Wang, Zheng-Sheng Lai, Tzu-Chi Hsu, Tung-Liang Lee, Yu-Chiau Shyu, Pei-Wen Hsiao, Liuh-Yow Chen, Trees-Juen Chuang, Chen-Hsin Albert Yu, Nah-Shih Liao, View ORCID ProfileChe-Kun James Shen
doi: https://doi.org/10.1101/2023.04.21.537849
Jing-Ping Wang
1The PhD Program for Neural Regenerative Medicine, Taipei Medical University, Taipei 115, Taiwan
2Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 115, Taiwan
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Chun-Hao Hung
1The PhD Program for Neural Regenerative Medicine, Taipei Medical University, Taipei 115, Taiwan
2Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 115, Taiwan
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  • ORCID record for Chun-Hao Hung
  • For correspondence: ckshen@gate.sinica.edu.tw yuchiaushyu@gmail.com libur777@hotmail.com
Yao-Huei Liou
2Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 115, Taiwan
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Ching-Chen Liu
2Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 115, Taiwan
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Kun-Hai Yeh
2Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 115, Taiwan
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Keh-Yang Wang
1The PhD Program for Neural Regenerative Medicine, Taipei Medical University, Taipei 115, Taiwan
2Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 115, Taiwan
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Zheng-Sheng Lai
2Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 115, Taiwan
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Tzu-Chi Hsu
1The PhD Program for Neural Regenerative Medicine, Taipei Medical University, Taipei 115, Taiwan
2Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 115, Taiwan
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Tung-Liang Lee
2Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 115, Taiwan
6Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung Branch, Keelung 204, Taiwan
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Yu-Chiau Shyu
2Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 115, Taiwan
3Department of Nursing, Chang Gung University of Science and Technology, Taoyuan City 333, Taiwan
6Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung Branch, Keelung 204, Taiwan
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  • For correspondence: ckshen@gate.sinica.edu.tw yuchiaushyu@gmail.com libur777@hotmail.com
Pei-Wen Hsiao
4Agricultural Biotechnology Research Center, Academia Sinica, Nankang, Taipei 115, Taiwan
5Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 115, Taiwan
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Liuh-Yow Chen
2Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 115, Taiwan
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Trees-Juen Chuang
7Genomics Research Center, Academia Sinica, Nankang, Taipei 115, Taiwan
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Chen-Hsin Albert Yu
2Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 115, Taiwan
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Nah-Shih Liao
2Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 115, Taiwan
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Che-Kun James Shen
1The PhD Program for Neural Regenerative Medicine, Taipei Medical University, Taipei 115, Taiwan
2Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 115, Taiwan
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  • ORCID record for Che-Kun James Shen
  • For correspondence: ckshen@gate.sinica.edu.tw yuchiaushyu@gmail.com libur777@hotmail.com
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Abstract

A causal relationship exists among the aging process, organ decay and dis-function, and the occurrence of various diseases including cancer. A genetically engineered mouse model, termed EklfK74R/K74R or Eklf(K74R), carrying mutation on the well-conserved sumoylation site of the hematopoietic transcription factor KLF1/ EKLF has been generated that possesses extended lifespan and healthy characteristics including cancer resistance. We show that the high anti-cancer capability of the Eklf(K74R) mice are gender-, age-and genetic background-independent. Significantly, the anti-cancer capability and extended lifespan characteristics of Eklf(K74R) mice could be transferred to wild-type mice via transplantation of their bone marrow mononuclear cells. Targeted/global gene expression profiling analysis has identified changes of the expression of specific proteins and cellular pathways in the leukocytes of the Eklf(K74R) that are in the directions of anti-cancer and/or anti-aging. This study demonstrates the feasibility of developing a novel hematopoietic/ blood system for long-term anti-cancer and, potentially, for anti-aging.

Competing Interest Statement

The authors have declared no competing interest.

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Posted April 21, 2023.
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Hematopoietic Transfer of the Anti-Cancer and Lifespan-Extending Capabilities of A Genetically Engineered Blood System
Jing-Ping Wang, Chun-Hao Hung, Yao-Huei Liou, Ching-Chen Liu, Kun-Hai Yeh, Keh-Yang Wang, Zheng-Sheng Lai, Tzu-Chi Hsu, Tung-Liang Lee, Yu-Chiau Shyu, Pei-Wen Hsiao, Liuh-Yow Chen, Trees-Juen Chuang, Chen-Hsin Albert Yu, Nah-Shih Liao, Che-Kun James Shen
bioRxiv 2023.04.21.537849; doi: https://doi.org/10.1101/2023.04.21.537849
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Hematopoietic Transfer of the Anti-Cancer and Lifespan-Extending Capabilities of A Genetically Engineered Blood System
Jing-Ping Wang, Chun-Hao Hung, Yao-Huei Liou, Ching-Chen Liu, Kun-Hai Yeh, Keh-Yang Wang, Zheng-Sheng Lai, Tzu-Chi Hsu, Tung-Liang Lee, Yu-Chiau Shyu, Pei-Wen Hsiao, Liuh-Yow Chen, Trees-Juen Chuang, Chen-Hsin Albert Yu, Nah-Shih Liao, Che-Kun James Shen
bioRxiv 2023.04.21.537849; doi: https://doi.org/10.1101/2023.04.21.537849

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