Nature Communications (Mar 2021)
Mutant ASXL1 induces age-related expansion of phenotypic hematopoietic stem cells through activation of Akt/mTOR pathway
- Takeshi Fujino,
- Susumu Goyama,
- Yuki Sugiura,
- Daichi Inoue,
- Shuhei Asada,
- Satoshi Yamasaki,
- Akiko Matsumoto,
- Kiyoshi Yamaguchi,
- Yumiko Isobe,
- Akiho Tsuchiya,
- Shiori Shikata,
- Naru Sato,
- Hironobu Morinaga,
- Tomofusa Fukuyama,
- Yosuke Tanaka,
- Tsuyoshi Fukushima,
- Reina Takeda,
- Keita Yamamoto,
- Hiroaki Honda,
- Emi K. Nishimura,
- Yoichi Furukawa,
- Tatsuhiro Shibata,
- Omar Abdel-Wahab,
- Makoto Suematsu,
- Toshio Kitamura
Affiliations
- Takeshi Fujino
- Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo
- Susumu Goyama
- Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo
- Yuki Sugiura
- Department of Biochemistry, Keio University School of Medicine, and Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO), Suematsu Gas Biology Project
- Daichi Inoue
- Human Oncology and Pathogenesis Program, Memorial Sloan−Kettering Cancer Center and Weill Cornell Medical College
- Shuhei Asada
- Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo
- Satoshi Yamasaki
- Laboratory of Molecular Medicine, Human Genome Center, The Institute of Medical Science, The University of Tokyo
- Akiko Matsumoto
- Laboratory of Molecular Medicine, Human Genome Center, The Institute of Medical Science, The University of Tokyo
- Kiyoshi Yamaguchi
- Division of Clinical Genome Research, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo
- Yumiko Isobe
- Division of Clinical Genome Research, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo
- Akiho Tsuchiya
- Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo
- Shiori Shikata
- Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo
- Naru Sato
- Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo
- Hironobu Morinaga
- Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University
- Tomofusa Fukuyama
- Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo
- Yosuke Tanaka
- Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo
- Tsuyoshi Fukushima
- Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo
- Reina Takeda
- Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo
- Keita Yamamoto
- Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo
- Hiroaki Honda
- Field of Human Disease Models, Major in Advanced Life Sciences and Medicine, Tokyo Women’s Medical University
- Emi K. Nishimura
- Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University
- Yoichi Furukawa
- Division of Clinical Genome Research, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo
- Tatsuhiro Shibata
- Laboratory of Molecular Medicine, Human Genome Center, The Institute of Medical Science, The University of Tokyo
- Omar Abdel-Wahab
- Human Oncology and Pathogenesis Program, Memorial Sloan−Kettering Cancer Center and Weill Cornell Medical College
- Makoto Suematsu
- Department of Biochemistry, Keio University School of Medicine, and Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO), Suematsu Gas Biology Project
- Toshio Kitamura
- Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo
- DOI
- https://doi.org/10.1038/s41467-021-22053-y
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 20
Abstract
ASXL1 mutations are frequently found in age-related clonal haemaotopoiesis (CH), but how they drive CH is unclear. Here the authors show that expression of C-terminal truncated ASXL1 in haematopoietic stem cells (HSCs) leads to Akt de-ubiquitination, activated Akt/mTOR signaling, and aberrant HSC proliferation.
