Human induced pluripotent stem cell-derived salivary gland organoids model SARS-CoV-2 infection and replication

Junichi Tanaka; Hidenobu Senpuku; Miho Ogawa; Rika Yasuhara; Shintaro Ohnuma; Koki Takamatsu; Takashi Watanabe; Yo Mabuchi; Shiro Nakamura; Shoko Ishida; Tomohiko Sadaoka; Takashi Takaki; Tatsuo Shirota; Toshikazu Shimane; Tomio Inoue; Takayoshi Sakai; Munemasa Mori; Takashi Tsuji; Ichiro Saito; Kenji Mishima

doi:10.1038/s41556-022-01007-6

Human induced pluripotent stem cell-derived salivary gland organoids model SARS-CoV-2 infection and replication

Junichi Tanaka, Hidenobu Senpuku, Miho Ogawa, Rika Yasuhara, Shintaro Ohnuma, Koki Takamatsu, Takashi Watanabe, Yo Mabuchi, Shiro Nakamura, Shoko Ishida, Tomohiko Sadaoka, Takashi Takaki, Tatsuo Shirota, Toshikazu Shimane, Tomio Inoue, Takayoshi Sakai, Munemasa Mori, Takashi Tsuji, Ichiro Saito, Kenji Mishima

研究成果: ジャーナルへの寄稿 › 学術論文 › 査読

21 被引用数 (Scopus)

抄録

Salivary glands act as virus reservoirs in various infectious diseases and have been reported to be targeted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the mechanisms underlying infection and replication in salivary glands are still enigmatic due to the lack of proper in vitro models. Here, we show that human induced salivary glands (hiSGs) generated from human induced pluripotent stem cells can be infected with SARS-CoV-2. The hiSGs exhibit properties similar to those of embryonic salivary glands and are a valuable tool for the functional analysis of genes during development. Orthotopically transplanted hiSGs can be engrafted at a recipient site in mice and show a mature phenotype. In addition, we confirm SARS-CoV-2 infection and replication in hiSGs. SARS-CoV-2 derived from saliva in asymptomatic individuals may participate in the spread of the virus. hiSGs may be a promising model for investigating the role of salivary glands as a virus reservoir.

本文言語	英語
ページ（範囲）	1595-1605
ページ数	11
ジャーナル	Nature Cell Biology
巻	24
号	11
DOI	https://doi.org/10.1038/s41556-022-01007-6
出版ステータス	出版済み - 11-2022
外部発表	はい

All Science Journal Classification (ASJC) codes

細胞生物学

UN SDG

この成果は、次の持続可能な開発目標に貢献しています

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10.1038/s41556-022-01007-6

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引用スタイル

Tanaka, J., Senpuku, H., Ogawa, M., Yasuhara, R., Ohnuma, S., Takamatsu, K., Watanabe, T., Mabuchi, Y., Nakamura, S., Ishida, S., Sadaoka, T., Takaki, T., Shirota, T., Shimane, T., Inoue, T., Sakai, T., Mori, M., Tsuji, T., Saito, I., & Mishima, K. (2022). Human induced pluripotent stem cell-derived salivary gland organoids model SARS-CoV-2 infection and replication. Nature Cell Biology, 24(11), 1595-1605. https://doi.org/10.1038/s41556-022-01007-6

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title = "Human induced pluripotent stem cell-derived salivary gland organoids model SARS-CoV-2 infection and replication",

abstract = "Salivary glands act as virus reservoirs in various infectious diseases and have been reported to be targeted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the mechanisms underlying infection and replication in salivary glands are still enigmatic due to the lack of proper in vitro models. Here, we show that human induced salivary glands (hiSGs) generated from human induced pluripotent stem cells can be infected with SARS-CoV-2. The hiSGs exhibit properties similar to those of embryonic salivary glands and are a valuable tool for the functional analysis of genes during development. Orthotopically transplanted hiSGs can be engrafted at a recipient site in mice and show a mature phenotype. In addition, we confirm SARS-CoV-2 infection and replication in hiSGs. SARS-CoV-2 derived from saliva in asymptomatic individuals may participate in the spread of the virus. hiSGs may be a promising model for investigating the role of salivary glands as a virus reservoir.",

author = "Junichi Tanaka and Hidenobu Senpuku and Miho Ogawa and Rika Yasuhara and Shintaro Ohnuma and Koki Takamatsu and Takashi Watanabe and Yo Mabuchi and Shiro Nakamura and Shoko Ishida and Tomohiko Sadaoka and Takashi Takaki and Tatsuo Shirota and Toshikazu Shimane and Tomio Inoue and Takayoshi Sakai and Munemasa Mori and Takashi Tsuji and Ichiro Saito and Kenji Mishima",

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year = "2022",

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doi = "10.1038/s41556-022-01007-6",

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Tanaka, J, Senpuku, H, Ogawa, M, Yasuhara, R, Ohnuma, S, Takamatsu, K, Watanabe, T, Mabuchi, Y, Nakamura, S, Ishida, S, Sadaoka, T, Takaki, T, Shirota, T, Shimane, T, Inoue, T, Sakai, T, Mori, M, Tsuji, T, Saito, I & Mishima, K 2022, 'Human induced pluripotent stem cell-derived salivary gland organoids model SARS-CoV-2 infection and replication', Nature Cell Biology, vol. 24, no. 11, pp. 1595-1605. https://doi.org/10.1038/s41556-022-01007-6

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AU - Watanabe, Takashi

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AU - Ishida, Shoko

AU - Sadaoka, Tomohiko

AU - Takaki, Takashi

AU - Shirota, Tatsuo

AU - Shimane, Toshikazu

AU - Inoue, Tomio

AU - Sakai, Takayoshi

AU - Mori, Munemasa

AU - Tsuji, Takashi

AU - Saito, Ichiro

AU - Mishima, Kenji

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Human induced pluripotent stem cell-derived salivary gland organoids model SARS-CoV-2 infection and replication

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All Science Journal Classification (ASJC) codes

UN SDG

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