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Salivary gland organoid culture maintains distinct glandular properties of murine and human major salivary glands

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  • Yeo-Jun Yoon

    (Yonsei University College of Medicine)

  • Donghyun Kim

    (Yonsei University College of Medicine)

  • Kwon Yong Tak

    (Korean Advanced Institute of Science and Technology)

  • Seungyeon Hwang

    (Yonsei University College of Medicine)

  • Jisun Kim

    (Yonsei University College of Medicine)

  • Nam Suk Sim

    (Yonsei University College of Medicine)

  • Jae-Min Cho

    (Yonsei University College of Medicine)

  • Dojin Choi

    (Yonsei University College of Medicine)

  • Yongmi Ji

    (National Institute of Dental and Craniofacial Research, NIH)

  • Junho K. Hur

    (Hanyang University)

  • Hyunki Kim

    (Yonsei University College of Medicine)

  • Jong-Eun Park

    (Korean Advanced Institute of Science and Technology)

  • Jae-Yol Lim

    (Yonsei University College of Medicine)

Abstract

Salivary glands that produce and secrete saliva, which is essential for lubrication, digestion, immunity, and oral homeostasis, consist of diverse cells. The long-term maintenance of diverse salivary gland cells in organoids remains problematic. Here, we establish long-term murine and human salivary gland organoid cultures. Murine and human salivary gland organoids express gland-specific genes and proteins of acinar, myoepithelial, and duct cells, and exhibit gland functions when stimulated with neurotransmitters. Furthermore, human salivary gland organoids are established from isolated basal or luminal cells, retaining their characteristics. Single-cell RNA sequencing also indicates that human salivary gland organoids contain heterogeneous cell types and replicate glandular diversity. Our protocol also enables the generation of tumoroid cultures from benign and malignant salivary gland tumor types, in which tumor-specific gene signatures are well-conserved. In this study, we provide an experimental platform for the exploration of precision medicine in the era of tissue regeneration and anticancer treatment.

Suggested Citation

  • Yeo-Jun Yoon & Donghyun Kim & Kwon Yong Tak & Seungyeon Hwang & Jisun Kim & Nam Suk Sim & Jae-Min Cho & Dojin Choi & Yongmi Ji & Junho K. Hur & Hyunki Kim & Jong-Eun Park & Jae-Yol Lim, 2022. "Salivary gland organoid culture maintains distinct glandular properties of murine and human major salivary glands," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30934-z
    DOI: 10.1038/s41467-022-30934-z
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    References listed on IDEAS

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    1. Junichi Tanaka & Miho Ogawa & Hironori Hojo & Yusuke Kawashima & Yo Mabuchi & Kenji Hata & Shiro Nakamura & Rika Yasuhara & Koki Takamatsu & Tarou Irié & Toshiyuki Fukada & Takayoshi Sakai & Tomio Ino, 2018. "Generation of orthotopically functional salivary gland from embryonic stem cells," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
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    3. Jennifer M. Rosenbluth & Ron C. J. Schackmann & G. Kenneth Gray & Laura M. Selfors & Carman Man-Chung Li & Mackenzie Boedicker & Hendrik J. Kuiken & Andrea Richardson & Jane Brock & Judy Garber & Debo, 2020. "Organoid cultures from normal and cancer-prone human breast tissues preserve complex epithelial lineages," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    4. Catarina P. Santos & Eleonora Lapi & Jaime Martínez de Villarreal & Laura Álvaro-Espinosa & Asunción Fernández-Barral & Antonio Barbáchano & Orlando Domínguez & Ashley M. Laughney & Diego Megías & Alb, 2019. "Urothelial organoids originating from Cd49fhigh mouse stem cells display Notch-dependent differentiation capacity," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
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