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.

Details

Title
Generation of orthotopically functional salivary gland from embryonic stem cells
Author
Tanaka, Junichi 1   VIAFID ORCID Logo  ; Ogawa, Miho 2   VIAFID ORCID Logo  ; Hojo, Hironori 3 ; Kawashima, Yusuke 4 ; Mabuchi, Yo 5   VIAFID ORCID Logo  ; Hata, Kenji 6 ; Nakamura, Shiro 7 ; Yasuhara, Rika 1 ; Takamatsu, Koki 8   VIAFID ORCID Logo  ; Tarou Irié 9   VIAFID ORCID Logo  ; Fukada, Toshiyuki 10 ; Sakai, Takayoshi 11   VIAFID ORCID Logo  ; Inoue, Tomio 7   VIAFID ORCID Logo  ; Nishimura, Riko 6   VIAFID ORCID Logo  ; Ohara, Osamu 12   VIAFID ORCID Logo  ; Saito, Ichiro 13 ; Ohba, Shinsuke 3 ; Tsuji, Takashi 2 ; Mishima, Kenji 1   VIAFID ORCID Logo 

1  Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Tokyo, Japan 
2  Laboratory for Organ Regeneration, RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Hyogo, Japan; Organ Technologies Inc., Tokyo, Japan 
3  Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, The University of Tokyo, Tokyo, Japan 
4  Laboratory for Integrative Genomics, RIKEN IMS, Yokohama, Kanagawa, Japan 
5  Department of Biochemistry and Biophysics, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan 
6  Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, Osaka, Japan 
7  Department of Oral Physiology, School of Dentistry, Showa University, Tokyo, Japan 
8  Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, Tokyo, Japan 
9  Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Tokyo, Japan; Division of Anatomical and Cellular Pathology, Department of Pathology, Iwate Medical University, Iwate, Japan 
10  Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Tokyo, Japan; Laboratory for Integrative Genomics, RIKEN IMS, Yokohama, Kanagawa, Japan; Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan 
11  Department of Oral-Facial Disorders, Osaka University Graduate School of Dentistry, Osaka, Japan 
12  Laboratory for Integrative Genomics, RIKEN IMS, Yokohama, Kanagawa, Japan; Department of Technology Development, Kazusa DNA Research Institute, Chiba, Japan 
13  Department of Pathology, Tsurumi University School of Dental Medicine, Yokohama, Kanagawa, Japan 
Pages
1-13
Publication year
2018
Publication date
Oct 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-06469-7
ProQuest document ID
2118356710
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.