TY - JOUR
T1 - Generation of orthotopically functional salivary gland from embryonic stem cells
AU - Tanaka, Junichi
AU - Ogawa, Miho
AU - Hojo, Hironori
AU - Kawashima, Yusuke
AU - Mabuchi, Yo
AU - Hata, Kenji
AU - Nakamura, Shiro
AU - Yasuhara, Rika
AU - Takamatsu, Koki
AU - Irié, Tarou
AU - Fukada, Toshiyuki
AU - Sakai, Takayoshi
AU - Inoue, Tomio
AU - Nishimura, Riko
AU - Ohara, Osamu
AU - Saito, Ichiro
AU - Ohba, Shinsuke
AU - Tsuji, Takashi
AU - Mishima, Kenji
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-018-06469-7
DO - 10.1038/s41467-018-06469-7
M3 - Article
C2 - 30310071
AN - SCOPUS:85054773410
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4216
ER -