Salivary Gland Tissue Recombination Can Modify Cell Fate [bulk RNA-seq]

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 roles of tissue interactions in cellular differentiation, we performed single cell RNA sequencing and imaging analyses of recombined tissues in which embryonic mouse salivary gland mesenchyme and epithelium were switched ex vivo. We found partial induction of molecules that define gland-specific acinar and myoepithelial cells in recombined salivary epithelium. Parotid epithelium (serous gland) recombined with submandibular mesenchyme (mixed serous-mucous, but predominantly mucous gland) 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 altered 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.