Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Tokyo, 142-8555, Japan.
Laboratory for Organ Regeneration, RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Hyogo, 650-0047, Japan.
Nat Commun. 2018 Oct 11;9(1):4216. doi: 10.1038/s41467-018-06469-7.
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.
类器官由多能干细胞生成，通过模拟器官发生过程，用于开发器官替代再生治疗。这些过程受到形态发生素信号和转录网络的严格调控。然而，参与包括唾液腺在内的外分泌腺器官发生的确切转录因子仍不清楚。在这里，我们确定了两个转录因子（Sox9 和 Foxc1）的特定组合，它们负责在类器官培养系统中将小鼠胚胎干细胞衍生的口腔外胚层分化为唾液腺原基。将诱导的唾液腺原基原位移植到唾液腺已被切除的小鼠体内后，诱导的唾液腺原基不仅表现出与正常小鼠胚胎唾液腺原基相似的形态和基因表达谱，而且还表现出成熟唾液腺的特征，包括唾液分泌。这项研究表明，可以从多能干细胞中诱导产生外分泌腺，用于器官替代再生治疗。
