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Title: Galactosyl carbohydrate residues on hematopoietic stem/progenitor cells are essential for homing and engraftment to the bone marrow
Authors: Takagaki, Soichiro
Yamashita, Rieko
Hashimoto, Noriyoshi
Sugihara, Kazushi
Kanari, Kanako
Tabata, Keisuke
Nishie, Toshikazu
Oka, Shogo  kyouindb  KAKEN_id
Miyanishi, Masanori
Naruse, Chie  kyouindb  KAKEN_id
Asano, Masahide  kyouindb  KAKEN_id
Author's alias: 高垣, 聡一郎
山下, 莉映子
橋本, 憲佳
杉原, 一司
金成, 香奈子
田畑, 佳祐
西江, 敏和
岡, 昌吾
宮西, 正憲
成瀬, 智恵
浅野, 雅秀
Keywords: Glycobiology
Haematopoietic stem cells
Issue Date: 9-May-2019
Publisher: Springer Science and Business Media LLC
Journal title: Scientific Reports
Volume: 9
Thesis number: 7133
Abstract: The role of carbohydrate chains in leukocyte migration to inflamed sites during inflammation and trafficking to the lymph nodes under physiological conditions has been extensively characterized. Here, we report that carbohydrate chains also mediate the homing and engraftment of hematopoietic stem/progenitor cells (HSPCs) to the bone marrow (BM). In particular, we found that transplanted BM cells deficient in β-1, 4-galactosyltransferase-1 (β4GalT-1) could not support survival in mice exposed to a lethal dose of irradiation. BM cells obtained from mice deficient in β4GalT-1 showed normal colony-forming activity and hematopoietic stem cell numbers. However, colony-forming cells were markedly rare in the BM of recipient mice 24 h after transplantation of β4GalT-1-deficient BM cells, suggesting that β4GalT-1 deficiency severely impairs homing. Similarly, BM cells with a point mutation in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene, encoding a key enzyme in sialic acid biosynthesis, showed mildly impaired homing and engraftment abilities. These results imply that the galactosyl, but not sialyl residues in glycoproteins, are essential for the homing and engraftment of HSPCs to the BM. These findings suggest the possibility of modifying carbohydrate structures on the surface of HSPCs to improve their homing and engraftment to the BM in clinical application.
Description: 骨髄移植における造血幹細胞の生着にはガラクトース糖鎖が必須であることを解明. 京都大学プレスリリース. 2019-05-16.
Rights: © The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
URI: http://hdl.handle.net/2433/241384
DOI(Published Version): 10.1038/s41598-019-43551-6
PubMed ID: 31073169
Related Link: https://www.kyoto-u.ac.jp/ja/research-news/2019-05-16-0
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