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Generation of orthotopically functional salivary gland from embryonic stem cells

Author

Listed:
  • Junichi Tanaka

    (Showa University)

  • Miho Ogawa

    (RIKEN Center for Biosystems Dynamics Research (BDR)
    Organ Technologies Inc.)

  • Hironori Hojo

    (The University of Tokyo)

  • Yusuke Kawashima

    (RIKEN IMS)

  • Yo Mabuchi

    (Tokyo Medical and Dental University)

  • Kenji Hata

    (Osaka University Graduate School of Dentistry)

  • Shiro Nakamura

    (Showa University)

  • Rika Yasuhara

    (Showa University)

  • Koki Takamatsu

    (Showa University)

  • Tarou Irié

    (Showa University
    Iwate Medical University)

  • Toshiyuki Fukada

    (Showa University
    RIKEN IMS
    Tokushima Bunri University)

  • Takayoshi Sakai

    (Osaka University Graduate School of Dentistry)

  • Tomio Inoue

    (Showa University)

  • Riko Nishimura

    (Osaka University Graduate School of Dentistry)

  • Osamu Ohara

    (RIKEN IMS
    Kazusa DNA Research Institute)

  • Ichiro Saito

    (Tsurumi University School of Dental Medicine)

  • Shinsuke Ohba

    (The University of Tokyo)

  • Takashi Tsuji

    (RIKEN Center for Biosystems Dynamics Research (BDR)
    Organ Technologies Inc.)

  • Kenji Mishima

    (Showa University)

Abstract

Organoids generated from pluripotent stem cells are used in the development of organ replacement regenerative therapy by recapitulating the process of organogenesis. These processes are strictly regulated by morphogen signalling and transcriptional networks. However, the precise transcription factors involved in the organogenesis of exocrine glands, including salivary glands, remain unknown. Here, we identify a specific combination of two transcription factors (Sox9 and Foxc1) responsible for the differentiation of mouse embryonic stem cell-derived oral ectoderm into the salivary gland rudiment in an organoid culture system. Following orthotopic transplantation into mice whose salivary glands had been removed, the induced salivary gland rudiment not only showed a similar morphology and gene expression profile to those of the embryonic salivary gland rudiment of normal mice but also exhibited characteristics of mature salivary glands, including saliva secretion. This study suggests that exocrine glands can be induced from pluripotent stem cells for organ replacement regenerative therapy.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06469-7
    DOI: 10.1038/s41467-018-06469-7
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    Cited by:

    1. 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.

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