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

被引：29

作者：

Tanaka, Junichi ^{[1
,2
,3
]}

Senpuku, Hidenobu ^{[4
,5
]}

Ogawa, Miho ^{[6
]}

Yasuhara, Rika ^{[1
]}

Ohnuma, Shintaro ^{[1
]}

Takamatsu, Koki ^{[7
]}

Watanabe, Takashi ^{[8
]}

Mabuchi, Yo ^{[9
]}

Nakamura, Shiro ^{[10
]}

Ishida, Shoko ^{[1
]}

Sadaoka, Tomohiko ^{[11
]}

Takaki, Takashi ^{[12
]}

Shirota, Tatsuo ^{[7
]}

Shimane, Toshikazu ^{[13
]}

Inoue, Tomio ^{[10
]}

Sakai, Takayoshi ^{[14
]}

Mori, Munemasa ^{[2
,3
]}

Tsuji, Takashi ^{[6
]}

Saito, Ichiro ^{[15
]}

Mishima, Kenji ^{[1
]}

机构：

[1] Showa Univ, Dept Oral Diagnost Sci, Div Pathol, Sch Dent, Tokyo, Japan

[2] Columbia Univ, Irving Med Ctr, Columbia Ctr Human Dev, New York, NY 10032 USA

[3] Columbia Univ, Irving Med Ctr, Dept Med, Div Pulm Allergy & Crit Care, New York, NY 10032 USA

[4] Natl Inst Infect Dis, Dept Bacteriol 1, Tokyo, Japan

[5] Nihon Univ, Dept Microbiol & Immunol, Sch Dent Matsudo, Chiba, Japan

[6] RIKEN Ctr Biosyst Dynam Res, Lab Organ Regenerat, Kobe, Hyogo, Japan

[7] Showa Univ, Dept Oral Surg, Sch Dent, Tokyo, Japan

[8] RIKEN Ctr Integrat Med Sci, Lab Integrat Genom, Yokohama, Kanagawa, Japan

[9] Juntendo Univ, Intractable Dis Res Ctr, Sch Med, Tokyo, Japan

[10] Showa Univ, Dept Oral Physiol, Sch Dent, Tokyo, Japan

[11] Kobe Univ, Grad Sch Med, Ctr Infect Dis, Div Clin Virol, Kobe, Hyogo, Japan

[12] Showa Univ, Ctr Electron Microscopy, Tokyo, Japan

[13] Showa Univ, Head & Neck Oncol Ctr, Tokyo, Japan

[14] Osaka Univ, Dept Oral Facial Disorders, Grad Sch Dent, Osaka, Japan

[15] Tsurumi Univ, Dept Pathol, Sch Dent Med, Yokohama, Kanagawa, Japan

来源：

NATURE CELL BIOLOGY | 2022年 / 24卷 / 11期

关键词：

RECEPTOR; ACE2;

D O I：

10.1038/s41556-022-01007-6

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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. Tanaka et al. generate human induced pluripotent stem cell-derived salivary gland organoids that serve as a model for salivary gland development and SARS-CoV-2 infection.

引用

页码：1595 / +

页数：25

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Junichi Tanaka
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[2] Author Correction: Human induced pluripotent stem cell-derived salivary gland organoids model SARS-CoV-2 infection and replication
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