Generation of orthotopically functional salivary gland from embryonic stem cells

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 Inoue, Riko Nishimura, Osamu Ohara, Ichiro Saito, Shinsuke Ohba, Takashi Tsuji and Kenji Mishima ()
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Junichi Tanaka: Showa University
Miho Ogawa: RIKEN Center for Biosystems Dynamics Research (BDR)
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
Toshiyuki Fukada: Showa 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
Ichiro Saito: Tsurumi University School of Dental Medicine
Shinsuke Ohba: The University of Tokyo
Takashi Tsuji: RIKEN Center for Biosystems Dynamics Research (BDR)
Kenji Mishima: Showa University

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06469-7

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DOI: 10.1038/s41467-018-06469-7

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