Project description:Our single-cell and bulk transcriptome analyses revealed striking molecular heterogeneity in the mesenchymal cells of embryonic submandibular and parotid salivary glands during bud initiation, including distinct mesodermal and neural crest-derived molecular signatures that foreshadow later functions.
Project description:Our single-cell and bulk transcriptome analyses revealed striking molecular heterogeneity in the mesenchymal cells of embryonic submandibular and parotid salivary glands during bud initiation, including distinct mesodermal and neural crest-derived molecular signatures that foreshadow later functions.
Project description:Branching organs, including the salivary and mammary glands, lung, and kidney, arise as epithelial buds that are morphologically very similar. However, the mesenchyme is known to guide epithelial morphogenesis and to help govern cell fate and eventual organ specificity. We performed single-cell transcriptome analyses of 14,441 cells from embryonic day 12 submandibular and parotid salivary glands to characterize their molecular identities during bud initiation. The mesenchymal cells were considerably more heterogeneous by clustering analysis than the epithelial cells. Nonetheless, distinct clusters were evident among even the epithelial cells, where unique molecular markers separated presumptive bud and duct cells. Mesenchymal cells formed separate, well-defined clusters specific to each gland. Neuronal and muscle cells of the 2 glands in particular showed different markers and localization patterns. Several gland-specific genes were characteristic of different rhombomeres. A muscle cluster was prominent in the parotid, which was not myoepithelial or vascular smooth muscle. Instead, the muscle cluster expressed genes that mediate skeletal muscle differentiation and function. Striated muscle was indeed found later in development surrounding the parotid gland. Distinct spatial localization patterns of neuronal and muscle cells in embryonic stages appear to foreshadow later differences in adult organ function. These findings demonstrate that the establishment of transcriptional identities emerges early in development, primarily in the mesenchyme of developing salivary glands. We present the first comprehensive description of molecular signatures that define specific cellular landmarks for the bud initiation stage, when the neural crest-derived ectomesenchyme predominates in the salivary mesenchyme that immediately surrounds the budding epithelium. We also provide the first transcriptome data for the largely understudied embryonic parotid gland as compared with the submandibular gland, focusing on the mesenchymal cell populations.
Project description:Salivary glands produce saliva and play essential roles in digestion and oral health. Pluripotent stem cell-derived (PSC) organoids provide a powerful platform for studying salivary gland development and developing new regenerative therapy. The previous protocol of PSC-derived salivary gland organoids required complicated manufacturing processes, which hampered the organoids for basic research and clinical application.Here, by mimicking the regulatory mechanism of developing salivary glands, we reported the differentiation of induced embryonic salivary glands (iE-SGs) from mouse embryonic stem cells by step-wise treatment of retinoic acid and FGF10. We showed that the iE-SGs recapitulated early morphogenetic events, including the thickening and invagination of the salivary gland placode, and then formed initial buds. The iE-SGs also differentiated into developing ducts structures and could develop to striated and excretory ducts when transplanted in vivo. RNA- seq revealed that iE-SGs had gene expression profiles similar to mouse embryonic SMGs. Thus, our study provided an easy and safe method to generate iE-SGs and offered possibilities for studying events during salivary gland morphogenesis in vitro
Project description:Salivary glands are composed of several types of cells, and each cell type is predicted to be involved in the carcinogenesis of different types of cancers. In this study, we performed single nucleus RNA-seq on 3 human salivary gland samples to clarify the gene expression profile of each complex cellular component of the salivary glands.
Project description:The aim of this study is characterize the gene expression of rat parotid, submandibular and sublingual glands, providing basic information for the salivary marker proteins.
Project description:Recent work indicates that salivary glands are able to constitutively recruit CD8+ T cells and retain them as tissue resident memory T cells (TRM), independently of local infection, inflammation or antigen. To understand the mechanisms supporting T cell recruitment to the salivary gland, we compared T cell migration to the salivary gland in mice infected or not with murine cytomegalovirus (MCMV), a herpesvirus that infects the salivary gland and promotes the accumulation of salivary gland TRM. We found that acute MCMV infection increased rapid T cell recruitment to the salivary gland, but that equal numbers of activated CD8+ 44 T cells eventually accumulated in both infected and uninfected glands. T cell recruitment to uninfected salivary glands depended on chemokines and the integrin α4. Several chemokines were expressed in the salivary glands of both infected and uninfected mice and many of these could promote the migration of MCMV-specific T cells in vitro. MCMV infection increased expression of chemokines that interact with the receptors CXCR3 and CCR5, but neither receptor was needed for T cell recruitment to the salivary gland during MCMV infection. Unexpectedly however, the chemokine receptor CXCR3 was critical for T cell accumulation in uninfected salivary glands. Together, these data suggest that CXCR3 and the integrin α4 mediate T cell recruitment to uninfected salivary glands, but that redundant mechanisms mediate T cell recruitment after MCMV infection.
Project description:Samples of acinar cell carcinoma (AciCC) of the salivary glands and paired normal salivary gland tissue were analyzed by whole transcriptome RNA-seq (n=10), whole genome sequencing (n=6), whole genome bisulfite sequencing (n=3) and ChIP-seq (H3K27ac, H3K4me3, H3K27me3, NR4A3, CTCF).