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, Kenji Mishima

Research output: Contribution to journalArticlepeer-review

100 Citations (Scopus)

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.

Original languageEnglish
Article number4216
JournalNature communications
Volume9
Issue number1
DOIs
Publication statusPublished - 01-12-2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy

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