Kyushu University [Yuya Kunisaki (Professor) Faculty of Medical Sciences, Research Center for Human Disease Modeling]

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Researcher information

Yuya Kunisaki
Professor
Research Center for Human Disease Modeling
Faculty of Medical Sciences
Last modified date：2024.04.15

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Country of degree conferring institution (Overseas)

Field of Specialization

Total Priod of education and research career in the foreign country

Research

Research Interests

Hematopoietic stem cell niches
keyword : Stem cells
2014.04～2030.03.

Current and Past Project

The aim of this project is to dissect the hematopoietic stem cell niches and to identify the hierarchy of mesenchymal cells, which regulate hematopoietic stem cell fate, by using bone marrow 3 dimensional imaging techniques.

Academic Activities

Reports

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1.	Yuya Kunisaki, Salazosulfapyridine induced hypersensitivity syndrome associated with reactivation of humanherpes virus 6., Internal Medicine, 2003.02.

Papers

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1.	Kidoya, Hiroyasu; Muramatsu, Fumitaka; Shimamura, Teppei; Jia, Weizhen; Satoh, Takashi; Hayashi, Yumiko; Naito, Hisamichi; Kunisaki, Yuya; Arai, Fumio; Seki, Masahide; Suzuki, Yutaka; Osawa, Tsuyoshi; Akira, Shizuo; Takakura, Nobuyuki, Regnase-1-mediated post-transcriptional regulation is essential for hematopoietic stem and progenitor cell homeostasis, 2019.03.
2.	Oshima, Tsuyoshi; Niwa, Yoshimi; Kuwata, Keiko; Srivastava, Ashutosh; Hyoda, Tomoko; Tsuchiya, Yoshiki; Kumagai, Megumi; Tsuyuguchi, Masato; Tamaru, Teruya; Sugiyama, Akiko; Ono, Natsuko; Zolboot, Norjin; Aikawa, Yoshiki; Oishi, Shunsuke; Nonami, Atsushi; Arai, Fumio; Hagihara, Shinya; Yamaguchi, Junichiro; Tama, Florence; Kunisaki, Yuya; Yagita, Kazuhiro; Ikeda, Masaaki; Kinoshita, Takayoshi; Kay, Steve A.; Itami, Kenichiro; Hirota, Tsuyoshi, Cell-based screen identifies a new potent and highly selective CK2 inhibitor for modulation of circadian rhythms and cancer cell growth, 10.1126/sciadv.aau9060. , 2019.01.
3.	Nakano, Michitaka; Kikushige, Yoshikane; Miyawaki, Kohta; Kunisaki, Yuya; Mizuno, Shinichi; Takenaka, Katsuto; Tamura, Shingo; Okumura, Yuta; Ito, Mamoru; Ariyama, Hiroshi; Kusaba, Hitoshi; Nakamura, Masafumi; Maeda, Takahiro; Baba, Eishi; Akashi, Koichi, Dedifferentiation process driven by TGF-beta signaling enhances stem cell properties in human colorectal cancer., 10.1038/s41388-018-0480-0., 2019.02.
4.	國﨑祐哉, Megakaryocytes regulate hematopoietic stem cell quiescence through CXCL4 secretion, NATURE MEDICINE, 20, 11, 1315-1320, 2014.11.
5.	Yuya Kunisaki, Defective fetal liver erythropoiesis and T lymphopoiesis in mice lacking the phosphatidylserine receptor. , blood, 103, 9, 3363-3364, 2004.05.
6.	Yuya Kunisaki, DOCK2 is required in T cell precursors for development of Valpha14 NK T cells., J Immunol, 176, 8, 4640-4645, 2006.04.
7.	Yuya Kunisaki, DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis. , J Cell Biol, 174, 5, 647-652, 2006.08.
8.	Yuya Kunisaki, Adrenergic nerves govern circadian leukocyte recruitment to tissues., Immunity, 10.1016/j.immuni.2012.05.021., 37, 2, 190-198, 2012.08.
9.	Yuya Kunisaki, Arteriolar niches maintain haematopoietic stem cell quiescence., Nature, 10.1007/s12185-014-1580-4, 502, 7473, 637-643, 2013.10.

Presentations

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1.	Yuya Kunisaki, NG2+ arteriolar parasites form niches for dormant hematopoietic stem cells, The 12th Stem Cell Research Symposium, 2014.05, Cell cycle quiescence is a critical feature contributing to hematopoietic stem cell (HSC) maintenance. Whether quiescence and proliferation of HSCs are regulated by spatially distinct niches is unclear. Whole-mount confocal immunofluorescence assessment revealed an evenly distributed sinusoidal network and rare small calibre arterioles specifically ensheathed by NG2+ perivascular cells, which were found predominantly in close proximity to the bone. We further found that ~40 % of HSCs were located within 20µm distance from arterioles. To assess the significance of this association, we developed a computational simulation, in which HSCs were randomly positioned on images of whole-mount prepared sterna. The observed mean distance to arterioles was statistically different from that of randomly placed HSCs. This suggests that the physical association of HSC with arterioles is significant. Prolonged quiescence is referred to as dormancy and tracked as label-retaining cells. We evaluated the spatial association of dormant HSCs with arterioles by pulse-chase experiments with EdU and found that significantly more EdU+ HSCs compared to total HSCs were located within 20µm distance from arterioles. To test the functional relevance, we evaluated HSC-arteriole associations in mice treated with 5FU. We found that on day 3 the vast majority of HSCs was closely associated with arterioles. These data together indicate that arterioles provide a milieu promoting quiescence for both HSCs and a safe harbor to protect them against genotoxic insults. To examine the function of NG2+ cells, we intercrossed NG2-creERTM with an inducible diphtheria toxin receptor (iDTR) line. Depletion of NG2+ cells changed HSC localization away from arterioles, and switched them into a non-quiescent state. In addition, we found a ~60% reduction in the number of HSCs in the BM. Taken together, these results suggest that periarteriolar NG2+ cells form dormant niches for HSCs and the presence of spatially distinct vascular niches for quiescent and non-quiescent (proliferating) HSCs in the BM. .
2.	Yuya Kunisaki, Bone Marrow Arteriolar Niches Maintain Hematopoietic Stem Cell Quiescence., アメリカ血液学会, 2012.12.
3.	Yuya Kunisaki, Circadian Adrenergic Regulation of Bone Marrow Endothelial Adhesion Molecule Expression Impacts Progenitor Recruitment and Engraftment Efficiency. , アメリカ血液学会, 2010.12.
4.	Yuya Kunisaki, Circadian Expression of Endothelial Selectins, Regulated by the Sympathetic Nervous System, Controls Peripheral Leukocyte Homeostasis., アメリカ血液学会, 2008.12.

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