Although mesenchyme is essential for inducing the epithelium of ectodermal organs, its precise role in organ-specific epithelial fate determination remains poorly understood. To elucidate the roles of tissue interactions in cellular differentiation, we performed single-cell RNA sequencing and imaging analyses on recombined tissues, where mesenchyme and epithelium were switched ex vivo between two types of embryonic mouse salivary glands: the parotid gland (a serous gland) and the submandibular gland (a predominantly mucous gland). We found partial induction of molecules that define gland-specific acinar and myoepithelial cells in recombined salivary epithelium. The parotid epithelium recombined with submandibular mesenchyme began to express mucous acinar genes not intrinsic to the parotid gland. While myoepithelial cells do not normally line parotid acini, newly induced myoepithelial cells densely populated recombined parotid acini. However, mucous acinar and myoepithelial markers continued to be expressed in submandibular epithelial cells recombined with parotid mesenchyme. Consequently, some epithelial cells appeared to be plastic, such that their fate could still be modified in response to mesenchymal signaling, whereas other epithelial cells appeared to be already committed to a specific fate. We also discovered evidence for bidirectional induction: transcriptional changes were observed not only in the epithelium but also in the mesenchyme after heterotypic tissue recombination. For example, parotid epithelium induced the expression of muscle-related genes in submandibular fibroblasts that began to mimic parotid fibroblast gene expression. These studies provide the first comprehensive unbiased molecular characterization of tissue recombination approaches exploring the regulation of cell fate.

中文翻译：

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唾液腺组织重组可以改变细胞命运。


尽管间充质对于诱导外胚层器官的上皮形成至关重要，但其在器官特异性上皮命运决定中的确切作用仍知之甚少。为了阐明组织相互作用在细胞分化中的作用，我们对重组组织进行了单细胞 RNA 测序和成像分析，其中间充质和上皮在两种类型的胚胎小鼠唾液腺之间进行离体转换：腮腺（一种浆液腺）和颌下腺（主要是粘液腺）。我们发现在重组唾液上皮中部分诱导了定义腺体特异性腺泡和肌上皮细胞的分子。与下颌下间质重组的腮腺上皮开始表达腮腺固有的粘液腺泡基因。虽然肌上皮细胞通常不会排列在腮腺腺泡上，但新诱导的肌上皮细胞密集地排列在重组的腮腺腺泡上。然而，粘液腺泡和肌上皮标志物在与腮腺间质重组的颌下上皮细胞中继续表达。因此，一些上皮细胞似乎是可塑的，因此它们的命运仍然可以响应间充质信号而改变，而其他上皮细胞似乎已经被赋予了特定的命运。我们还发现了双向诱导的证据：异型组织重组后，不仅在上皮中而且在间充质中都观察到转录变化。例如，腮腺上皮诱导下颌下成纤维细胞中肌肉相关基因的表达，这些基因开始模仿腮腺成纤维细胞的基因表达。 这些研究首次对探索细胞命运调节的组织重组方法进行了全面、公正的分子表征。