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Human induced pluripotent stem cell-derived salivary gland organoids model SARS-CoV-2 infection and replication.
Tanaka, Junichi; Senpuku, Hidenobu; Ogawa, Miho; Yasuhara, Rika; Ohnuma, Shintaro; Takamatsu, Koki; Watanabe, Takashi; Mabuchi, Yo; Nakamura, Shiro; Ishida, Shoko; Sadaoka, Tomohiko; Takaki, Takashi; Shirota, Tatsuo; Shimane, Toshikazu; Inoue, Tomio; Sakai, Takayoshi; Mori, Munemasa; Tsuji, Takashi; Saito, Ichiro; Mishima, Kenji.
  • Tanaka J; Division of Pathology, Department of Oral Diagnostic Sciences, Showa University School of Dentistry, Tokyo, Japan. jtanaka@dent.showa-u.ac.jp.
  • Senpuku H; Columbia Center for Human Development and Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA. jtanaka@dent.showa-u.ac.jp.
  • Ogawa M; Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan.
  • Yasuhara R; Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Chiba, Japan.
  • Ohnuma S; Laboratory for Organ Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
  • Takamatsu K; Division of Pathology, Department of Oral Diagnostic Sciences, Showa University School of Dentistry, Tokyo, Japan.
  • Watanabe T; Division of Pathology, Department of Oral Diagnostic Sciences, Showa University School of Dentistry, Tokyo, Japan.
  • Mabuchi Y; Department of Oral Surgery, Showa University School of Dentistry, Tokyo, Japan.
  • Nakamura S; Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Ishida S; Intractable Disease Research Centre, Juntendo University School of Medicine, Tokyo, Japan.
  • Sadaoka T; Department of Oral Physiology, Showa University School of Dentistry, Tokyo, Japan.
  • Takaki T; Division of Pathology, Department of Oral Diagnostic Sciences, Showa University School of Dentistry, Tokyo, Japan.
  • Shirota T; Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan.
  • Shimane T; Center of Electron Microscopy, Showa University, Tokyo, Japan.
  • Inoue T; Department of Oral Surgery, Showa University School of Dentistry, Tokyo, Japan.
  • Sakai T; Head and Neck Oncology Center, Showa University, Tokyo, Japan.
  • Mori M; Department of Oral Physiology, Showa University School of Dentistry, Tokyo, Japan.
  • Tsuji T; Department of Oral-Facial Disorders, Osaka University Graduate School of Dentistry, Osaka, Japan.
  • Saito I; Columbia Center for Human Development and Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
  • Mishima K; Laboratory for Organ Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
Nat Cell Biol ; 24(11): 1595-1605, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2077059
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Induced Pluripotent Stem Cells / COVID-19 Limits: Animals / Humans Language: English Journal: Nat Cell Biol Year: 2022 Document Type: Article Affiliation country: S41556-022-01007-6

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Induced Pluripotent Stem Cells / COVID-19 Limits: Animals / Humans Language: English Journal: Nat Cell Biol Year: 2022 Document Type: Article Affiliation country: S41556-022-01007-6